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Category Archives: Black/White Issues
It's been a long time since I last blogged, but Trump's election left me speechless. Then I read the latest Southern Poverty Law Center's Intelligence Report on white supremacists and was suddenly struck by how pathetic their beliefs are. I'm better because my skin is white? Skin color isn't even one of my accomplishments. It's like little kids boasting "I'm older than you are." Wouldn't it be more valid to base one's worth on something internal? Probably that's what experimenters realized when they tried to correlate white skin with larger brains, more refined morality, etc. Their attempts, now discredited, are an admission that skin color is a feeble basis for superiority.
Do we need white supremacy to compensate for our individual disappointments? My mother based her superiority on the triple bulwark of race, ethnicity, and religion. We were WASPS, "not Catholic, not Irish," she often added, to reinforce the point. But mother had few personal accomplishments, and her ambition was to be rich and a member of high society. She was thrilled when I dated the grandson of IBM's founder, ate steak with his family, and drove around his property in an antique car. She was furious when I turned down his invitation to go yachting because I'd already promised the day to a young man of lower class.
I can understand that she resented my failure to bring her status. I can understand that she was not content with having kept me well-fed, clothed, and educated. I don't understand what kept her from trying to find herself and to take pride in her own accomplishments. By ninth grade, I had an inkling of what I might accomplish and no longer needed to rely on being a WASP. But perhaps personal disappointments—unemployment, poverty, and a sense that the American dream is no longer possible— lie behind today's resurgence of white supremacists.
Of course, supremacy denotes power. For our own safety, we'd like to be members of the group in power, and, in America, that's people with white skin. I've certainly benefited, and I'm well aware of the institutional injustices that people of color have been powerless to prevent. It's natural to fear that people who don't look like us won't share our interests and so will trample us if given power. White people, black people, Latinos, Asians, Muslims—all of us want to protect ourselves. Trump's "Make America great again" was a familiar appeal to white supremacy. But did white people win?
Trump really represents Wall Street, corporate interests, and billionaires. Look at his cabinet nominees—certainly mostly white (and male) but all members of the 1%. Look at his policies. Trumpcare would have reduced by millions the number of people who have healthcare while letting each of the nation's 400 richest families save $7 million per year. Medicare, Medicaid, and social security are on the chopping block. Investment brokers who handle retirement funds will no longer have to put their clients' interests ahead of their own compensation or company profits. Banks may risk our savings. The Environmental Protection Agency is being decimated, and global warming, which threatens our existence, is denied.
The 1% is now supreme, the group with power. They do not share our interests, and they will trample us. People of color will be hurt the most, as usual, but so will the rest of us. For all our whiteness, we are watching our social safety nets disintegrate while the richest among us get tax breaks.
White supremacists have been duped. Skin color has nothing to do with values. If we want supremacy and its power to protect, we must band together with people who may not look like us but who share our interests. We'll need a platform that rises above the divisiveness of race, ethnicity, and religion—a platform based on the need for shelter, sustenance, and security. And we must vow to vote in such numbers in 2018 that no elected official dare ignore us. Paradoxically, our success will give each of us a sense of personal accomplishment.
This entry was posted in Black/White Issues, Culture and Society, Politics, Race and tagged 1%, political power, SPLC, Trump, white supremacy on April 26, 2017 by Chrystal Schivell.
I'm Racist
Recently I was told by a person of color that I'd ignored racist comments made by my white friends at a meeting we'd both attended. I was amazed—mortified. Why hadn't I heard or recognized the racist remarks? How could my friends have made such remarks? The accusation seemed based on a huge misunderstanding.
I asked whether my accuser had assumed we were talking about race. I begged for the specific words used so that I could address the issue. But she replied only that, no, there was no misunderstanding. She hadn't made assumptions, and she found it disheartening but predictable that I, like everyone else, would not want to lose my position and prestige or to address microaggressions. She advised me to be honest when looking at my friends and to recognize that it's comforting to look around a room where everyone looks like me and assume they're not racist. Clearly, she was disappointed in me.
I take seriously the criticism and counsel of a black person. I've learned enough about white privilege to realize that I and my friends might unwittingly be at fault. And microaggressions are tricky—sometimes intended to be complimentary to an individual but always demeaning to that person's ethnicity or race. ("Courtney, I never see you as a black girl." " Are you really Asian?" "Are you sure you have the right room? This is an honors section.") We could have tripped up. I am disappointed in myself.
But was my accuser right? When I'd told a former colleague and friend from Trenton High, a woman who is black, that in retirement I'd been attending a discussion group about race and white privilege, she fairly shouted at me "Why are you wasting your time?" I protested that I was learning from black people in the group. "They're all victims. Move on!" she said in disgust as she hung up. I felt disappointed in myself then, too.
At Trenton High we rarely talked about race and never about white privilege—though that same colleague laughingly told me that, when I arrived at Trenton High, she'd thought, "White woman…? Probably can't get a job anywhere else." At Trenton High, values trumped race; black and white idealists battled the black and white staff members who preferred the status quo. Ironically, after I'd retired and begun attending discussion groups, a second black colleague complained that I thought too much about race. I can't seem to please everyone, but I'm still more anxious to please black people than white people.
Am I racist? I guess that depends on whom I ask. Some black people perceive racism where others don't. Some insist "Never tell me to 'Get over it.' " Others cry "Move on." But black people don't think alike and don't have to. White people don't.
What now? I know better than to continue questioning my recent accuser about her perception of my racism. Such dismissiveness would only bolster her contention that I'm unaware of my privilege. Of course, I don't want to be racist. It would be helpful to know exactly what alerted her to my friends' racism, but I will probably never know. I'm grateful to have a diversity of black voices in my life and to have learned that no one black person speaks for all black people. So I will take my accuser's criticism and counsel seriously—and move on.
This entry was posted in Black/White Issues, Culture and Society, Race, Trenton, Uncategorized and tagged "Get over it", "Let's move on", black people as victims of slavery, diversity of black voices, privilege, Trenton High on March 3, 2016 by Chrystal Schivell.
My recent posts have been about giving money, but when a friend expressed awe at my husband's and my generosity, I felt embarrassed. I hadn't meant to boast but rather to point out a need. And I know that my friend gives generously of her time. I've overstated the importance of money.
The gift of time is, despite the clock, immeasurable. My friend has become a surrogate mother to the mentally handicapped daughter of a friend who died years ago. Each night the young woman calls. My friend listens to the young woman recount her day and reassures her that she cares. It's tedious but necessary. I know because I get calls from a similarly handicapped fellow I taught almost 50 years ago. I listen to the litany about his trips to Walmart, the mileage on his car, his problems on the job (with nary a question about me). But he calls only once a month. Listening every night is true generosity, and I admire my friend's devotion.
Another friend has chided me for seeming to belittle the time given by Princetonians who volunteer in Trenton with TASK, "People and Stories," and soccer. I apologize. Time given to others—whether individuals or organizations—is time taken from oneself. And driving to Trenton adds more time. Of course, time spent with others can be rewarding. I enjoyed my time teaching so much that sometimes I'd forget it was payday, and the school secretary would have to wave my paycheck to catch my attention as I clocked out—but only sometimes. Nowadays I devote a day each week to visiting my paralyzed friend in her nursing home. Time spent shopping for her and sitting with her eats into time to accomplish what I'd like to get done, but I love our visits. She does too. Time is a gift.
Then I remember her exclamation of joy, "I can look out my window!" For a year, she had lain in bed or been placed in a wheelchair facing the TV. To see outside required turning her head because she was unable to move her chair. Medicare had promised a mobilized wheelchair as long as she stayed in her home, and we tried to keep her there until it arrived. But bureaucracy delayed delivery; money for round-the-clock care ran out; and she had to go into a home as a Medicaid recipient. Medicare doesn't give motorized chairs to people in nursing homes, and even the appeals of our Congressmen couldn't produce a waiver. Finally I bought a Jazzy—a bright-red, motorized chair—and unwittingly gave her the simple joy of looking out her window.
My thesis collapses. Which is worth more: the time I spend with her or the time she spends looking out her window and driving independently around the nursing home because I bought her "Jazzy"? I guess the answer is: give time, but, if needed, and if you can, give money too.
This entry was posted in Black/White Issues, Culture and Society, Trenton and tagged charity, Medicare, People and Stories, Princetonians, TASK, volunteering, wheelchair on February 22, 2016 by Chrystal Schivell.
Giving – With Strings
Since the publication of my article "Volunteering in Trenton," I've found a young man, recently home from the army, who needs financial help. He'd like to become an EMT and then go on to college to become a social worker. He was on the way to his goal— had gotten a job near a bus route, saved money, bought a used car, and then found a better-paying job to which he drove fellow workers. But the car broke down one morning on the way to work. He called at 7:15, but my husband and I, cozy in bed, suggested they take a taxi. We weren't getting up to drive to Hamilton and rescue them. It turned out that he and his fellow workers were fired for failing to show up at work. Without savings to fix the car, he fell into depression, rarely leaving his bedroom in his mother's house in Trenton. Six weeks later I learned the whole story.
I could have suggested that he buck up, borrow bus fare, and start all over again. But since I'd just told my readers that the "effective help" Trentonians need is money, or at least a ride, I'd have felt like a hypocrite. Besides, depression is a disease. Instead, I suggested to my husband that we get the car fixed and pay the tuition for the EMT course so he could start immediately. He'd be responsible for finding a job that fit with his class schedule, maintaining the car, and getting his financial house in order for the future.
My husband surprised me. He balked. "We don't have the money."
"How much do we give to charity?"
"Couldn't we make him our charity for 2016?"
"Yes, but how do we know he won't waste it?"
"How do we know for sure that the charities we give to don't waste it?"
"OK, but what if he doesn't finish the EMT course, and we lose our investment?"
"I think we can trust him. We've known him since he was a little kid."
"Don't you remember the Land Rover?"
Ah yes, the Land Rover! Almost twenty years ago, we supported one of my Trenton High students through college and then added his wife and her tuition, a car, and, eventually, their child. Of course, maintaining such a household wasn't cheap, but it was an excellent investment. They earned degrees, got good jobs, and finally were on their own. Then the first car they bought was a new Land Rover. We were dismayed. Why something so ostentatious? Hadn't we taught them not to waste money?
But it went deeper. I was reminded of the stereotype of black people and cars and felt a chill. Suddenly the young man who called me "Mom" was not like me: he didn't share my values. For my husband it was a slap in the face. The person he'd been supporting at my request now drove a more expensive car than he'd ever owned. Given all the money he'd shelled out, the Land Rover should have and could have been his—if he'd wanted one. That Land Rover—synonymous with being taken advantage of.
Now, in our conversation about helping this second young, black man with his car and EMT tuition, my husband uses words like "hand out" and "soft touch." But is it a hand out or a hand up? Can we just leave someone to drown in depression, perhaps become suicidal? After all, pulling oneself up by one's bootstraps is physically impossible. You'd give him food—the Trenton Area Soup Kitchen is one of our charities. But isn't it better to teach him to fish? And won't having a car to get him to class for EMT training be like teaching him to fish?
What about returning to the army? Sure, they'd look after him, but is that his choice? Isn't the problem that poor people have so little choice? Wasn't the army his only option when he graduated from Trenton High? How depressing to be back at square one!
What about getting a bang for our charity buck? We just saw a segment on the PBS Newshour comparing the cost effectiveness of vaccinating dozens of children versus delivering one baby in Nepal by C-section. Yes, but didn't at least one doctor defend everyone's right to health care? How can anyone say "No" face to face?
I, too, hate to feel used, but we had no contract that said, "You can't buy a Land Rover with your own money." Isn't any investment, whether in people or the stock market, a risk? Is a gift with strings a gift? Is giving about the giver or the recipient?
The young man has told me that he will disappoint himself, as well as us, if he doesn't complete the EMT course. I want to trust him. I do trust him. And finally, my husband trusts me. We'll see.
This entry was posted in Black/White Issues, Culture and Society, Trenton and tagged army, charity, hand outs, taking advantage on February 9, 2016 by Chrystal Schivell.
Volunteering in Trenton
The following two articles were published in the Princeton Packet In October, 2015. The first is by my writing instructor, Anne Neumann, the second by me. We were both responding to a question about volunteering in Trenton that had been raised at a forum we attended together. Our responses, however, are quite different.
by Anne Waldron Neumann
On September 20 the Princeton Community Democratic Organization (PCDO) sponsored a panel on racism: a praiseworthy effort. But eight panel members and two topics—the Black Lives Matter movement generally and racism in Princeton specifically—made the resulting discussion somewhat disconnected and overly general.
Given two minutes each for initial comments, a Princeton historian got as far as black homeowners being displaced by Palmer Square in the early 1930s, and by Paul Robeson Place in the late 1950s. Young panel members described social media as disseminating both productive exchanges and vitriol. Ministers discussed religion's role in overcoming racism. One panel member said that white people use "playing the race card" to mean taking unfair advantage, while black people know that race taints the entire deck.
Final questions for the panel were collected in writing. Several people asked about a clergyman's suggestion that something like South Africa's Truth and Reconciliation Commission could address Princeton's racialist history. Someone else asked about Hillary Clinton's belief that government can't change hearts and minds. ("I don't believe you change hearts. You change laws, you change allocation of resources, you change the way systems operate," Ms. Clinton said.)
And one anonymous audience member, presuming extreme economic and therefore class disparities between many Princetonians and many Trentonians, asked how to be involved in Trenton in ways that "might be effective and comfortable." Since none of the panel members addressed the question, the moderator asked the largely white audience instead.
As I see it, the question was both crucial and contradictory. Several audience members did describe volunteering in ways they found effective and comfortable: serving food in the Trenton Area Soup Kitchen, participating in "People and Stories," and combining a passion with outreach by coaching soccer. But wouldn't being meaningfully helpful in Trenton entail, for most white people, being profoundly uncomfortable? Wouldn't it clarify both the disadvantages many Trentonians suffer and the white privilege that's usually invisible?
"White privilege" includes systems that determine wealth over generations: going to the "right" school, acquiring the "right" cultural capital, getting the "right" job, and (probably, with your parents' help) buying the "right" house—one that will never lose value precipitously. White privilege also includes seeming trivialities such as, if you're well-spoken, never being called "articulate" and never being asked to be a spokesperson for your "race."
Racial sensitivity training is designed to make white privilege visible. An African-American friend described participating in a well-known exercise in which workmates stepped forward if they'd ever been asked to show identification when paying by credit card, been stopped for driving too slowly (perhaps even in their own neighborhood), and so on. By the end of the exercise, the black employees had crossed the room while white ones had hardly budged.
It's easy to think of ways to get white people across the room in this exercise: just ask the good opposite of the usual bad questions. If you don't know any jokes about people like you, take a step forward. If you own your own silverware, take a step forward (take another step if it has at least three initials on each piece, and a baby step if the initials are from a previous generation).
But what about good things that might get black people across the room? Step forward if you can sit on your front porch and know a neighbor will stop by to chat. Or bad things that would cause white people to step forward? "If your child ever told you to f*** off and lived to tell the tale, take one giant step," my friend suggested.
Clearly, cultural differences as well as economic ones may divide white and black folks. So, to return to the PCDO forum question, can privileged white people genuinely help underprivileged black people? White volunteers might give some black people more experiences—hopefully positive—of interacting with white people. White volunteers might gain experiences—surely sometimes painful—of interacting with black people. As I see it, volunteering in Trenton would at best change hearts and open minds.
I do think government can also help change hearts and minds. The presidency is a bully pulpit, after all. But, by and large, I'm with Hillary Clinton. Not that Princetonians shouldn't volunteer in Trenton. But we need to change the laws and systems that determine how resources are allocated. We need, as Thomas Piketty argues, to tax not just return on capital but its possession. We need to make rent partly tax deductible, not just interest on mortgage payments.We need equal treatment under law enforcement. We need universal voter registration. We need campaign finance reform. We need voting districts set by bipartisan commissions.
In short, we need the healthful society that promotes healthful hearts and minds. We need to make volunteering in Trenton both comfortable and unnecessary.
Volunteering in Trenton, Part 2
by Chrystal Schivell
In last week's "As I See It" column, Anne Neumann discussed a recent Princeton Community Democratic Organization (PCDO) panel "Getting Beyond Racism." Like Anne, I was troubled by the question about "how to be involved in Trenton in ways that might be effective and comfortable." As I listened to audience members mention TASK, "People and Stories," and soccer, I remembered situations I'd encountered in my 23 years' teaching at Trenton Central High School:
A young lady in Trenton High's nursing program has prepared diligently for the test that will certify her as a nursing assistant and allow her to work in a hospital after graduation. The test is on a Saturday, and her father has agreed to drive her. The father fails to show up; a taxi is out of the question. She misses the test and is not certified.
Tamara, the vice-president of student government and a gifted student, is accepted at Syracuse University, her dream school. Buoyed by monetary awards she received at graduation, she attends freshman year. Back home, her mother is in a traffic accident, a new car is needed, and insurance rates go up. Tamara's family can no longer afford Syracuse, and she enrolls at MCCC.
A Trenton High senior has been accepted at Georgetown and runs to show a black teacher the letter. "Why did you choose such an expensive school?" is her response, not "Bravo!" But she's intuitive: no guidance counselor has explained to this bright young man how to apply for scholarships. His regal bearing belies his financial ignorance and need as the son of a single mom, recently arrived from Jamaica, who works as a domestic. At Georgetown, one week, his meal ticket runs out. He's "hangry" (hungry and angry). Friends ask him to join them for drinks. He covers with "No, you guys run along. I have to study." But he cannot study, cannot sleep. He remembers he has $4 in his bank account, but in those days the minimum withdrawal from an ATM is $5. He goes to the gym to work out, finds a $5 bill on the basketball court, buys a TV dinner, and credits God for his luck.
A colleague asks me whether I have any candle stubs. Her electricity has been cut off.
The effective help these people needed was money—in some cases advice—but primarily money. Were the members of the forum's audience aware of the need? Did they feel a need to address it?
"Trenton" is a code word for "poor black people." Let's examine what happens if we split "poor" and "black." Probably we white Princetonians who become involved in Trenton see our involvement as enriching the lives of black folk. It soothes our guilt. But if, as panelists noted, race is a fiction—we are all members of the human race—would we be equally satisfied helping poor white people? Is our emphasis on poverty or race? I've known black teachers and counselors who cared little about enriching the lives of their black students; some even resented their success, jealous that the students might be getting ahead of them: "You're from the projects. You'll never become a doctor." My point: effective involvement in Trenton means addressing its poverty.
Anne Neumann called for legal and systemic changes to lessen economic disparity. I agree, but meanwhile, for me, the disparity is immediate and has faces. A Trenton High colleague often said, "You can't save all the whales," his analogy for dealing with the poverty we witnessed. No, but my husband and I saved two.
My advice is to find among the poor children in "People and Stories" or on the soccer team one with whom you have a natural affinity. Ask permission of the parent(s) to become financially involved in their child's life. If they agree, start with emergency funds for that taxi or TV dinner. Give your phone number and be prepared to drive the child to tests, science fairs, or out-of-state competitions. Suggest joining the parent(s) for parent-teacher conferences. When necessary, provide tutoring and pay for SAT, and AP tests. Invite the child to your home—and to Washington, New York, and Philadelphia. Use your experience to help the child plan for college and then check that the scholarship money and student loans really do cover the child's needs. The list will go on: will you help with housing if the child goes to graduate school? What if the child needs a car to get to work? It's the commitment that's crucial—being there for that phone call if things go awry.
Money is never a comfortable topic. And if you treat your financially adopted child as you would treat your own child, you may find that you spend very generously. But you will have been effective. The enrichment you gave initially with soccer and "People and Stories" will enhance your adopted child's future—not dead end in frustration.
This entry was posted in Black/White Issues, Culture and Society, Politics, Race, Trenton and tagged Hillary Clinton, reparations, sensitivity training, volunteering on February 1, 2016 by Chrystal Schivell.
My series "Overcoming Racism" feels pointless when today's theme is "Black Lives Matter." Since I began my blog a year ago, the country seems to have become more divided. Black people have been forced to take as their own every black male, regardless of his guilt or innocence, because law enforcement and the judiciary—from Ferguson and Chicago to New York and Baltimore—protect their own from scrutiny and responsibility.
I feel hopeless. Will white America interpret "Black Lives Matter" as divisive or as an appeal to make black folk our own? Can we expect professional organizations—police or teachers' unions—to weed out those individuals whose actions defame their professions? (That Baltimore State's Attorney Marilyn J. Mosby charged the six officers involved in Freddie Gray's arrest offers some hope, but, sure enough, the Fraternal Order of Police immediately protested.) And when politicians are backed by billionaires and lobbyists, whose interests do they serve?
With admiration, I watch my husband grieve for the victims of the earthquake in Nepal as if they were his own. With impatience, I pass Trenton Central High School—surrounded by fencing since last fall but not yet demolished, much less rebuilt—and grieve for the year already lost to its students, who are now scattered around town in buildings without libraries, science labs, or gyms. Young minds matter. When will we care for the least among us as if they were our own?
This will be my last post for a while.
This entry was posted in Black/White Issues, Culture and Society, Race, Trenton and tagged Baltimore, Black Lives Matter, Freddie Gray, Marilyn Mosby, Trenton Central High School on May 4, 2015 by Chrystal Schivell.
Overcoming Racism – Recognizing Sensationalism
To make sense of our universe, we categorize. I needed to see all black adults as clones of Dr. Martin Luther King, to put them in a favorable box. Likewise, I needed to see my Trenton High School students as good. Interestingly, one of the security guards at Trenton High, a person of color who also categorized, tried to make sure I did. In my first week, she told me,"My kids are good kids," her gesture encompassing every kid in school. Perhaps she was afraid I'd pegged them as bad or difficult. After all, most suburban people, white and black, called me a saint for working at Trenton High. They read The Trentonian, whose masthead was "Love us, hate us, read us." Some of the school's negative press was valid, but a mild disturbance in the cafeteria would likely be reported in an inflammatory front-page headline.
Sometimes, The Trentonian had a point. During a summer vacation in Hawaii, I picked up two volcanic rocks for my earth science class. I'd heard about Pele's revenge – the streak of bad luck inflicted by Pele, the goddess of fire, for taking them – but I figured it was only two rocks and for a good cause. Then my father-in-law developed cancer, my daughter broke up with her boyfriend, the refrigerator failed, and my husband's brand new car was stolen from our driveway and totaled during the police chase that followed. That September, back at Trenton High, I was telling my first-period class about Pele's revenge when a young man piped up, "Was it a red Accord?"
I gasped, "How did you know?"
The young man explained that as part of an initiation he and other black friends had been required to go to Princeton in the dead of night to steal Hondas, but he said earnestly, "We would never have taken it, Mrs. Schivell, if we'd known it was yours!"
In contrast, my wallet was stolen at Trenton High on two occasions―in spite of the fact that my students knew it was mine. The first time was when I floated among rooms. I had to leave my purse temptingly visible on the teacher's desk because the desk wasn't mine, and the drawers were locked. My principal, who was black, advised me to put my purse out of sight, but where? My wallet vanished when I was called out of the room for a minute, but I didn't notice until class was over. The next day, I chastised the four members of the class, one of whom had to have been responsible and all of whom knew who was. "I trusted you!" I protested. No one confessed. Their spokesman told me I'd been asking for it.
Perhaps these students, unlike my car thief, had little affection for me. I'd just returned from a year's furlough and hadn't had time to rebuild my reputation. On the other hand, the young woman who most likely took my wallet on the second occasion may have had other motives. She'd returned to the classroom after school was over, while I was tutoring one of the young men from her class. My purse was on a chair, out of sight under my desk. She walked over to the chair, then turned and played at the chalkboard behind my desk, and finally left, saying to the young man that she'd wait for him so they could take the bus together. Focused on tutoring, I paid little attention to her. But later, when the young man had gone, her strange behavior triggered my suspicions, and I checked my purse. She was picked up and searched by security, but no wallet was found. The young man was not searched. Two days later, a bus driver returned the wallet—missing only cash. Perhaps she took the wallet because she wanted to impress the young man or because they were in cahoots or perhaps because she wanted to get back at me for being hard on her in my attempt to elicit her best efforts in class.
But what about all the other classes? Even in my own room, I often forgot to hide my purse; yet hundreds of students over my 23 years at Trenton High were not tempted. For these hundreds of students I have no stories. Respect for property doesn't make for stories, doesn't beg for a motive. Ironically, we don't ask kids why they behave well, just why they behave badly. The deviant "you asked for it" or "stealing's OK except from friends" seems more interesting.
It did feel weird to know a car thief and to have him point out in the auditorium the young man, his arm in a cast, who'd driven and totaled my husband's Accord. Such stories make titillating cocktail party conversation, as does the one about the young man who flashed a $50 bill when I gave him his free lunch tickets—just to show he was gaming the system. But I and the media are guilty of sensationalism when we tell these stories. So are the people who want to read them. The truth is reassuringly boring: although a very few Trenton High students couldn't be trusted, most were good kids, just as the security guard promised.
This entry was posted in Black/White Issues, Culture and Society, Race, Trenton and tagged black culture, black students, media on May 1, 2015 by Chrystal Schivell.
Overcoming Racism – Understanding Black People (The Truth)
To understand what black people (at least in America) have in common, white people must recognize what we ourselves have in common: our privilege. From childhood, I knew I was privileged because Mother told me I was an aristocrat and better than even most other white people. As a child, I believed her. Although we were poor, I went to the best private schools on scholarship—in hand-me-down uniforms. And, when Greenwich friends invited me to their mansions and country clubs, where the only black people were employees, I learned I was more privileged than black people, too. When my grandmother died, we inherited wealth amassed by generations before us, including wealth from an ancestor who, though a Northerner, had sold tent canvas to Southern rebels during the Civil War. Inheriting is like winning the lottery, but it is an advantage, like education, denied to a people who started as slaves and were later limited to share-cropping and menial jobs.
Many white people don't enjoy my particular privileges, but, whether or not we realize it, we whites all enjoy privileges black people don't. Peggy McIntosh's well-known White Privilege: Unpacking the Invisible Knapsack lists 50 examples, such as, "Whether I use checks, credit cards or cash, I can count on my skin color not to work against the appearace of financial reliability" and "I can turn on the television or open to the front page of the paper and see people of my race widely represented." My favorite is, "I am never asked to speak for all the people of my racial group." It mirrors my last post about white people's misguided eagerness to "understand" black people based on characteristics.
Black people don't share characteristics any more than white people do. But black people do share experiences—the experience of being second-class citizens, just as white people share privilege. To understand black people we must recognize that all have experienced—or anticipate experiencing—an inequity based on color. Some are blatant lies—"Sorry, the apartment was just rented." Some are what are now called microagressions—"I never see you as a black girl." Each item on Peggy McIntosh's list represents an instance in which a black person is not treated as well as someone who's white. Her list reminds us that, in a society still dominated by white males, only white men can feel entirely comfortable. If we want to understand black people, we must acknowledge the truth of these experiences.
The black experience is unlike that of other immigrants in America. Black people were the only immigrants to come here against their will rather than to escape famine and persecution or to find better jobs. Marriage among slaves could be forbidden; mothers, fathers, and children could be split apart and sold to different slave owners; learning to read was risky. Their color made them stand out. Few blacks could elude the slave catcher. Nor could they elude the prevailing myth, designed to justify their enslavement, that black people were inferior. The free labor provided by slavery was the foundation of the South's economy. Southern cotton fed Northern mills, and America profited. The economic benefits and social evils of slavery, whether in America or elsewhere, cannot be denied.
The painful legacy of slavery and its economic benefits persists in the perception that black people are different from, if not inferior to, other groups—even that they require well-intentioned "understanding." And, not surprisingly, the people in power since colonial times—white men—want to keep their power. Thus racism persists as a strong undercurrent in politics and the economy. Black people know they can occasionally expect to be treated as second-class citizens. And Africans who've just arrived in the States, even those who are wealthy and unfamiliar with racism, learn the same lesson. After all, only white men can feel entirely comfortable, knowing that they will be considered for employment and certain they will never be told that towels are needed in the restroom.
Understanding black people means acknowledging America's history of white power and black enslavement. Some black people emphasize our painful legacy: "America was built on the backs of our people." To them, I can't say "Get over it," even though I'd like to spare myself a guilt that I, as an individual, feel I don't deserve. I can't dismiss those individuals who see themselves as victims because black people, by virtue of their color, are victims of America's history, just as white people, like me, are beneficiaries. Other black people adopt a "Let's move on" attitude. That attitude is easier on me, but I shouldn't assume it means we've reached a post-racial society. The past remains alive in Ferguson and on Wall Street. The "Let's move on" advocates know that much work remains before black people are assured of first-class citizenship. If we want to understand black people, we must be prepared, as we listen to each black person we meet, to accept the validity of either perspective.
This entry was posted in Black/White Issues, Culture and Society, Politics, Race and tagged "Get over it", "Let's move on", black people as victims of slavery, Peggy McIntosh, second-class citizenship, slavery, White Privilege on March 22, 2015 by Chrystal Schivell.
Overcoming Racism – Understanding Black People (The Fallacy)
In our attempt to overcome the racism we've been taught, many of us older white liberals try to "understand" black people. I know I did. I went to teach at Trenton High believing that all the black teachers and administrators would be like Martin Luther King, Jr. They'd be devoted to improving the lives of their students. Eager to think the best of—but totally unfamiliar with—black people, I chose a stellar example to define my "they." And whenever my colleagues turned out not to be clones of Dr. King, I was confused and disappointed.
White people who remain racist have often chosen a negative stereotype to describe black people. A childhood acquaintance who still lives in Greenwich, where I grew up, employed a black woman to look after her own children. Yet, when I visited and told her that I worked with black people, she said, "Isn't it awful the way they raise their kids!" I was shocked by this racist comment. She certainly didn't know enough black people to generalize about how "they" raised their kids. I also wondered why she hadn't chosen the nanny she'd trusted for years as her definition of "they."
My acquaintance and I were both misguided. We wouldn't have tried to understand or describe white people. Why try with black people? What I didn't recognize at the time was that, although my acquaintance was certainly racist, I exercised a more subtle form of racism myself. I wished that those black mothers who didn't raise their children well would realize they were giving black people a bad name. "Don't you know what white people are thinking?" was my silent plea. "Don't you know how many of us generalize from individuals to groups, from 'you' to 'they'?"
Liberal white folk don't want to think badly of black people and so don't like to be reminded that some black individuals actually do bad things. After Ferguson, I heard white friends complain that Michael Brown should have gotten out of the street, shouldn't have used the "f" word, shouldn't have taken those cigarettes, should have backed off. I think they complain partly because better behavior might have saved Michael Brown's life but perhaps partly because, even though they side with Michael Brown, they would have preferred to support a model black teenager. Michael Brown's aggressiveness makes them uncomfortable. Yet, if Michael Brown were their son's troubled white friend (their own son, of course, would never lock horns with a cop), wouldn't they overlook his behavior and concentrate only on the outrageous over-reaction of the police?
Black professionals know that, because of America's history of racism, they must be better than their white counterparts to achieve the same success. We white liberals acknowledge that this pressure is unfair. Yet we pressure a Michael Brown or a black welfare mother because we fear that their behavior will feed the racism of other white people—and perhaps our own. That pressure is racist because we don't ask the same of the in-your-face white teenager or white welfare mother. Their behavior is no reflection on us—unless, of course, black people generalize from the individual to the race, as many white people do. Yet if I don't want to be held responsible for the actions of the Ku Klux Klan, I can't expect a black person to be responsible for the behavior of other black people.
White people are good, bad, smart, dumb, beautiful and ugly, and so are black people. White people who've grown up in integrated communities know this from childhood. I didn't. But, I was fortunate to work with a cross-section of black people. I learned it then.
This entry was posted in Black/White Issues, Race, Trenton and tagged black professionals, generalizing from individuals to race, Martin Luther King, Michael Brown, welfare mother on March 7, 2015 by Chrystal Schivell.


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I would like to receive pricing for the following item: Compel Moda Task Chair.


There are currently 4 homes available in Planterra Ridge with an average price of $463,725. For availability or more information about homes for sale in Planterra Ridge call Gerald Wessels at 678-263-8817 .
Planterra Ridge is located in Peachtree City GA, Fayette County. There are currently 4 homes active and for sale inside the neighborhood with the average price being $463,725. The number of homes for sale in Planterra Ridge is always changing so if you see a home you like and you would like to schedule a time to take a look please give me a call at 678-263-8817.


text:
1124.60 Handler's value of milk.
§ 1124.60 Handler's value of milk.
For the purpose of computing a handler's obligation for producer milk, the market administrator shall determine for each month the value of milk of each handler with respect to each of the handler's pool plants and of each handler described in § 1000.9(c) with respect to milk that was not received at a pool plant by adding the amounts computed in paragraphs (a) through (h) of this section and subtracting from that total amount the value computed in paragraph (i) of this section. Unless otherwise specified, the skim milk, butterfat, and the combined pounds of skim milk and butterfat referred to in this section shall result from the steps set forth in § 1000.44 (a), (b), and (c), respectively, and the nonfat components of producer milk in each class shall be based upon the proportion of such components in producer skim milk. Receipts of nonfluid milk products that are distributed as labeled reconstituted milk for which payments are made to the producer-settlement fund of another Federal order under § 1000.76 (a)(4) or (d) shall be excluded from pricing under this section.
(a) Class I value.
(1) Multiply the hundredweight of skim milk in Class I by the Class I skim milk price; and
(2) Add an amount obtained by multiplying the pounds of butterfat in Class I by the Class I butterfat price.
(b) Class II value.
(1) Multiply the pounds of nonfat solids in Class II skim milk by the Class II nonfat solids price; and
(2) Add an amount obtained by multiplying the pounds of butterfat in Class II times the Class II butterfat price.
(c) Class III value.
(1) Multiply the pounds of protein in Class III skim milk by the protein price;
(2) Add an amount obtained by multiplying the pounds of other solids in Class III skim milk by the other solids price; and
(3) Add an amount obtained by multiplying the pounds of butterfat in Class III by the butterfat price.
(d) Class IV value.
(1) Multiply the pounds of nonfat solids in Class IV skim milk by the nonfat solids price; and
(2) Add an amount obtained by multiplying the pounds of butterfat in Class IV by the butterfat price.
(e) Multiply the pounds of skim milk and butterfat overage assigned to each class pursuant to § 1000.44(a)(11) and the corresponding steps of § 1000.44(b) by the skim milk prices and butterfat prices applicable to each class.
(f) Multiply the difference between the current month's Class I, II, or III price, as the case may be, and the Class IV price for the preceding month by the hundredweight of skim milk and butterfat subtracted from Class I, II, or III, respectively, pursuant to § 1000.44(a)(7) and the corresponding step of § 1000.44(b);
(g) Multiply the difference between the Class I price applicable at the location of the pool plant and the Class IV price by the hundredweight of skim milk and butterfat assigned to Class I pursuant to § 1000.43(d) and the hundredweight of skim milk and butterfat subtracted from Class I pursuant to § 1000.44(a)(3) (i) through (vi) and the corresponding step of § 1000.44(b), excluding receipts of bulk fluid cream products from plants regulated under other Federal orders and bulk concentrated fluid milk products from pool plants, plants regulated under other Federal orders, and unregulated supply plants.
(h) Multiply the difference between the Class I price applicable at the location of the nearest unregulated supply plants from which an equivalent volume was received and the Class III price by the pounds of skim milk and butterfat in receipts of concentrated fluid milk products assigned to Class I pursuant to § 1000.43(d) and § 1000.44(a)(3)(i) and the corresponding step of § 1000.44(b) and the pounds of skim milk and butterfat subtracted from Class I pursuant to § 1000.44(a)(8) and the corresponding step of § 1000.44(b), excluding such skim milk and butterfat in receipts of fluid milk products from an unregulated supply plant to the extent that an equivalent amount of skim milk or butterfat disposed of to such plant by handlers fully regulated under any Federal milk order is classified and priced as Class I milk and is not used as an offset for any other payment obligation under any order.
(i) For reconstituted milk made from receipts of nonfluid milk products, multiply $1.00 (but not more than the difference between the Class I price applicable at the location of the pool plant and the Class IV price) by the hundredweight of skim milk and butterfat contained in receipts of nonfluid milk products that are allocated to Class I use pursuant to § 1000.43(d).

redpajama_set_name: RedPajamaCommonCrawl


text:
BioDrugs
pp 1–12 | Cite as
Biological Characterization of SB3, a Trastuzumab Biosimilar, and the Influence of Changes in Reference Product Characteristics on the Similarity Assessment
Jae Hee Lee
Kyungyeol Paek
Jae Hyon Moon
Sunyoung Ham
Jinsu Song
Seokkyun Kim
First Online: 12 June 2019
SB3 has been developed as a trastuzumab biosimilar, a therapeutic monoclonal antibody targeted to human epidermal growth factor receptor 2 (HER2), and approved by the European Commission and United States (US) Food and Drug Administration (FDA). During the developmental period of a biosimilar, setting an appropriate quality target is critical for assessing the similarity of the biosimilar product to the reference product. A stepwise approach should be taken to assessing similarity, beginning with extensive characterization of the reference product to establish the quality target.
In this study, we evaluated the similarity of SB3 to the reference product and the impact of changes in the biological profile of the reference product on similarity assessment.
Analytical similarity was assessed with defined test procedures in terms of critical quality attributes (CQAs) that could affect efficacy, potency, and safety, as well as for the non-CQAs that are related to process consistency. The quality target was established using up to 154 lots of European Union (EU)- and US-sourced Herceptin® (reference product), analyzed during the developmental period of SB3.
Trends of the EU- and US-sourced reference product showed that the biological profile exhibited two marked changes for Fc-related attributes, and then recovered to pre-change quality level. Since the similarity range set by pre-change lots was considered most relevant, the changed lots were excluded from establishing the similarity range, which resulted in tightened acceptance criteria. As shown in the results of similarity assessment using the stringent quality target ranges, SB3 exhibits highly similar functional activities compared to the reference product in terms of both CQAs and non-CQAs.
SB3 has been developed as a trastuzumab biosimilar approved in the EU and USA, and its manufacturing process is deemed to be robust and well-controlled within stringent quality target ranges.
Up to 154 lots of Herceptin® (reference product) were analyzed for the characterization of the trastuzumab biosimilar SB3. After two sequential changes in the biological profile in both EU- and US-sourced reference product, the attributes recovered to pre-change levels.
Considering the influence of biological profile changes on the range, the quality target was tightened for similarity assessment by excluding the lots where the biological profile had changed.
SB3 demonstrated high similarity in critical biological quality attributes, including Fab-related biological activities, effector functions such as direct mechanism of action-related antibody-dependent cell-mediated cytotoxicity (ADCC) and Fcγ receptor IIIa binding, and neonatal Fc receptor (FcRn) binding that may affect its half-life.
A biosimilar is a biological medicinal product with structural and functional properties that are highly similar to an authorized and already approved original biological drug, and whose pharmacokinetics and clinical activity are shown to be similar in a comparative clinical trial [1]. The European Medicines Agency (EMA) and United States (US) Food and Drug Administration (FDA) have developed biosimilar guidelines, with a requirement to demonstrate the totality of evidence including analytical, non-clinical, and clinical similarity [2, 3, 4, 5, 6, 7]. Analytical similarity in structural and functional properties is critical to expect the absence of any meaningful difference in clinical outcomes. Based on this fundamental assumption, a similarity assessment should be performed by a stepwise approach, starting with extensive physicochemical and biological characterization of both the biosimilar and the reference product [2, 3]. Studies for analytical similarity should be based on analytical data with defined test procedures and acceptance criteria for the reference product's critical quality attributes (CQAs) that could affect efficacy, potency, and safety, as well as for non-CQAs that are related to process consistency [4].
Human epidermal growth factor receptor 2 (HER2) is a membrane-bound receptor protein that promotes cell growth and division when activated by ligand binding. In approximately 20–25% of breast cancers, HER2 is overexpressed, associated with faster growth of the cancer and a higher recurrence rate [8]. Trastuzumab is a therapeutic monoclonal antibody (mAb) of the IgG1 subclass with a kappa light chain, specifically targeted to HER2. Since trastuzumab was developed by humanizing the parental murine antibody "4D5," it contains a human framework region and the complementarity-determining regions of a murine antibody that binds to the domain IV region of HER2 [9]. HER2 is activated by dimerization, which leads to the activation of the Ras/Raf/mitogen-activated protein kinase (MAPK), phosphoinositide 3-kinase (PI3K)/Akt, and phospholipase Cγ (PLCγ)/protein kinase C pathways required for the cell proliferation [10, 11]. The mechanism of action (MoA) of trastuzumab is known to be its inhibition of proliferation of HER2-overexpressing cells by blocking MAPK and PI3K/Akt pathways [12, 13]. Another major mechanism of trastuzumab is to attract immune cells to HER2-overexpressing tumor sites, called antibody-dependent cell-mediated cytotoxicity (ADCC) [14, 15]. Upon antigen binding to mAbs, effector functions are mediated by their Fc part that binds to Fcγ receptor (FcγR) IIIa (FcγRIIIa, also known as CD16a). The N-glycosylation pattern of mAbs influences the binding affinity of its Fc part to FcγRIIIa. Trastuzumab also induces HER2 internalization and degradation through binding to HER2 [16].
Trastuzumab was approved by the US FDA in 1998 and by the European Commission (EC) in 2000 for the treatment of certain patients with breast cancers overexpressing HER2 under the trade name Herceptin® (hereafter called "reference product") [17]. In addition, as a combination therapy, trastuzumab plus chemotherapy regimen has become the standard of care for the treatment of HER2-positive breast cancers, providing significant clinical benefit in adjuvant settings against early as well as advanced or metastatic breast cancers [18, 19, 20].
SB3 was developed as a trastuzumab biosimilar by Samsung Bioepis Co., Ltd. (Incheon, Republic of Korea), and approved by the EC in Nov 2017 and by the US FDA in Jan 2019, for the treatment of HER2-positive breast cancer and HER2-overexpressing gastric cancer. In the Republic of Korea and Australia, SB3 was approved by the Ministry of Food and Drug Safety and the Therapeutic Goods Administration in November 2017 and December 2018, respectively. In accordance with the International Conference on Harmonisation (ICH) Q8 (R2) guideline, a risk assessment was conducted to establish the CQAs for SB3 on the basis of the MoA for trastuzumab and the analytical capability of state-of-the-art methods. Risk priority number (RPN) is scored for the impact and uncertainty of attributes on efficacy and safety, and applied to evaluate the CQAs. The CQAs of SB3 were established based on impacts not only on HER2 binding and the subsequent anti-proliferation effect, but also on its effector functions associated with the Fc domain in general.
To demonstrate the similarity of SB3 to the reference product, an extensive analytical characterization was executed based on the quality target profile established during the developmental period. During the characterization study of SB3, up to 154 lots of reference product were analyzed, and two sequential changes in Fc-related attributes such as the sum value of %afucose + %high mannose, FcγRIIIa binding, ADCC, and %galactosylation (G1F + G2F) were observed in both EU- and US-sourced reference product expiring between August 2018 and December 2019 [21]. Herein, the analytical similarity of SB3 was assessed with the stringent quality target ranges set by excluding the lots of reference product demonstrating biological profile changes. The results demonstrate that SB3 is highly similar to the reference product in terms of biological quality attributes.
2 Materials and Methods
2.1 Materials
EU- and US-sourced reference product (up to 154 lots) were purchased from local distributors and then stored according to the manufacturer's instructions. The reference standard for the bioassays was prepared from EU-sourced reference product and used for characterization of the reference products and SB3. The CellTiter-Blue® and CytoTox-Glo® kits were obtained from Promega (Madison, WI, USA). The PNGase-F kit was obtained from New England Biolabs (NEB, Ipswich, MA, USA). The 2-aminobenzamide (2-AB) labelling kit for N-glycan analysis was obtained from Ludger (Oxfordshire, UK). Glutathione (GSH)-coated donor beads, human IgG-conjugated acceptor beads, and streptavidin-coated donor beads were obtained from PerkinElmer (Waltham, MA, USA). The glutathione-S-transferase (GST)-tagged FcγRIIIa and HER2-Fc were obtained from Biogen (Cambridge, MA, USA). Biotin-labelled neonatal Fc receptor (FcRn) was obtained from Biogen (Cambridge, MA, USA). C1q protein was obtained from Quidel (San Diego, CA, USA). Anti-C1q horseradish peroxidase (HRP) conjugated antibody (catalog number AB46191) was obtained from Abcam (Cambridge, MA, USA). Statistical analysis and graphical comparison were performed with Minitab statistic software package (Leadtools Technologies Inc., version 18.1.0, Charlotte, NC, USA).
2.2 Cell Lines and Cell Culture
SKBR3 cells were obtained from American Type Culture Collection (ATCC, Manassas, VA, USA) and incubated at 37 °C, 5% CO2 in McCoy's 5A (Gibco, Grand Island, NY, USA) containing 10% fetal bovine serum (FBS) (Hyclone, Logan, UT, USA). BT474 cells were obtained from ATCC and incubated at 37 °C, 5% CO2 in Dulbecco's Modified Eagle Medium: Nutrient Mixture F-12 (DMEM/F12, Gibco) containing 10% FBS. NK92-CD16 cells were obtained from Biogen (Cambridge, MA, USA) and incubated at 37 °C, 5% CO2 in Myelocult H5100 (Stemcell Technology, Vancouver, Canada) containing human interleukin-2 (Cell Signaling Technology, Beverly, MA, USA) and puromycin (Gibco).
2.3 Anti-proliferation Assay
The anti-proliferation potency was measured by CellTiter-Blue® cell viability assay kit (Promega) according to manufacturer's instruction. BT474 cells were incubated with ten serially diluted concentrations (0.008–1.0 μg/mL) of trastuzumab for 4 days at 37 °C, 5% CO2 in DMEM/F12 containing 10% FBS. The relative number of viable cells was quantified by measuring the fluorescence (excitation at 560 nm and emission at 590 nm) using a SpectraMax® M3 (Molecular Devices, San Jose, CA, USA). Data were analyzed using Parallel Line Analysis 2.0 (PLA) software (Stegmann Systems GmbH, Rodgau, Germany) to calculate relative anti-proliferation potency.
2.4 ADCC Assay
The ADCC assay was performed to assess Fc-related biological activity of trastuzumab against a HER2-overexpressing human breast cancer cell line (SKBR3). NK92-CD16 cells, a human natural killer cell line expressing CD16, were used as effector cells. Experimentally, trastuzumab was incubated with SKBR3 and NK92-CD16 cells in flat-bottom 96-well plates for 4 h at 37 °C, 5% CO2 in McCoy's 5A medium. After incubation, the SKBR3/NK92-CD16/sample mixture was incubated with a luminogenic peptide substrate (alanyl-alanyl-phenylalanyl-aminoluciferin; AAF-Glo Substrate) as a part of the CytoTox-Glo® kit. The luminescence signals (dead cell signals) were quantified by an Envision™ Multilabel Plate Reader (PerkinElmer). Data were analyzed by using PLA software to calculate relative ADCC potency.
2.5 HER2 Binding Assay
The competitive inhibitory HER2 binding assay was performed using time-resolved fluorescence resonance energy transfer (FRET) technology. When donor chromophore absorbs 340-nm wavelength light, it transfers 615-nm energy to an acceptor chromophore. Then, the acceptor chromophore emits longer wavelength light, and the detector accepts a 665-nm wavelength light. In this system, 12 concentrations (0.0488–100 μg/mL) of trastuzumab were incubated with a fixed volume of Europium chelate-labeled trastuzumab (donor chromophore) and Cy5-labeled HER2 (acceptor chromophore) in assay diluent [1 × phosphate-buffered saline (PBS), 0.1% bovine serum albumin (BSA), and pH 7.4]. The mixture was then incubated at 25 °C for 1 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) at a wavelength of 665 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.6 C1q Binding Assay
The C1q binding assay was performed to assess Fc-related biological activity of trastuzumab using sandwich enzyme-linked immunosorbent assay (ELISA). In this system, 96-well plates were coated with seven concentrations (0.391–25 μg/mL) of trastuzumab and incubated at 37 °C for 1 h. Then, the plate was blocked using blocking buffer and incubated at room temperature for 1 h. After blocking, a fixed concentration of C1q (Quidel) solution was added to the plate and the plate was incubated at room temperature. After incubation, fixed concentration of C1q-HRP antibody (Abcam) was added to the plate and the plate was incubated at room temperature. Using 3,3′,5,5′-tetramethylbenzidine (TMB) ELISA substrate (Sigma-Aldrich, St. Louis, MO, USA), C1q binding activity was quantified by measuring the absorbance at 450 nm using a SpectraMax® M3 (Molecular Devices). Data were analyzed by using PLA software to calculate the relative binding activity.
2.7 FcRn Binding Assay
The FcRn binding assay was performed to assess Fc-related biological activity of trastuzumab using Alphascreen™ technology with active donor and acceptor beads. With excitation, a photosensitizer in a donor bead converts ambient oxygen to reactive singlet oxygen. The singlet oxygen species reacts with thioxene compounds in the acceptor bead to generate a chemiluminescent signal that emits at 370 nm. In this system, 12 concentrations (0.021–200 μg/mL) of trastuzumab were incubated with a fixed volume of streptavidin-coated donor/human IgG-conjugated acceptor beads and biotin-labelled FcRn in assay diluent (20 mM 4–morpholineethanesulfonic acid, 150 mM NaCl, 0.1% BSA, pH 5.8). The mixture was incubated at 22 °C for 2 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) with excitation at 680 nm and reading emission at 520–620 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.8 FcγRIa Binding Assay
The competitive inhibitory FcγRIa binding assay was performed using time-resolved FRET technology. In this system, 12 concentrations (0.0257–150 μg/mL) of trastuzumab were incubated with a fixed volume of Europium chelate-labeled trastuzumab (donor chromophore) and Cy5-labeled FcγRIa (acceptor chromophore) in assay diluent (1 × PBS, 0.1% BSA, and pH 7.4). The mixture was then incubated at 25 °C for 1 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) at a wavelength of 665 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.9 FcγRIIa Binding Assay
The FcγRIIa binding assay was performed to assess Fc-related biological activity of trastuzumab using Alphascreen™ technology. In this system, 12 concentrations (0.26–166.67 μg/mL) of trastuzumab were incubated with a fixed volume of GSH-coated donor/human IgG-conjugated acceptor beads and GST-tagged FcγRIIa. The mixture was incubated at 22 °C for 2.0 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) with excitation at 680 nm and reading emission at 520–620 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.10 FcγRIIb Binding Assay
The FcγRIIb binding assay was performed to assess Fc-related biological activity of trastuzumab using Alphascreen™ technology. In this system, 12 concentrations (0.8–500 μg/mL) of trastuzumab were incubated with a fixed volume of GSH-coated donor/human IgG-conjugated acceptor beads and GST-tagged FcγRIIb. The mixture was incubated at 22 °C for 2.0 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) with excitation at 680 nm and reading emission at 520–620 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.11 FcγRIIIa Binding Assay
The FcγRIIIa binding assay was performed to assess Fc-related biological activity of trastuzumab using Alphascreen™ technology. In this system, 12 concentrations (0.0488–100 μg/mL) of trastuzumab were incubated with a fixed volume of GSH-coated donor/human IgG-conjugated acceptor beads and GST-tagged FcγRIIIa. The mixture was incubated at 22 °C for 3.5 h with moderate agitation. After incubation, the fluorescent signal was obtained from the Envision™ Multilabel Plate Reader (PerkinElmer) with excitation at 680 nm and reading emission at 520–620 nm. Data were analyzed by using PLA software to calculate the relative binding activity.
2.12 Glycosylation Profile by 2-Aminobenzamide Labeling and HILIC-UPLC Analysis
N-glycan profiles were analyzed using a hydrophilic interaction liquid chromatography–ultra-performance liquid chromatography (HILIC-UPLC) system (Waters, Milford, MA, USA). For quantitative determination, 100 μg of sample was denatured using sodium dodecyl sulfate (SDS) and dithiothreitol (DTT) in the PNGase-F enzyme kit (NEB) at 100 °C for 10 min, and treated with PNGase F to release N-glycans. The released N-glycans were separated using protein precipitation with cold ethanol, and the supernatant was dried. The dried N-glycans were then labelled with 2-AB for 3 h using a LudgerTag™ 2-AB glycan labeling kit (Ludger). Samples were injected onto a UPLC BEH glycan column (2.1 mm × 150 mm, 1.7 μm). The labeled N-glycans were separated at a flow rate of 0.5 mL/min with mobile phase A (50 mM ammonium formate) and mobile phase B (100% acetonitrile). The signal was detected using a fluorescence detector (Waters) at the excitation wavelength of 330 nm and the emission wavelength of 420 nm. Empower™3 software (Waters) was used for data processing and calculating the relative peak area.
3.1 Risk Assessment and CQA Classification
To evaluate the criticality of product quality attributes for SB3, a trastuzumab biosimilar functional risk assessment was conducted. The potential impact of individual attributes on product potency, efficacy, and safety was scored as well as the uncertainty regarding the impact assessment of the attributes. Based on RPN values scored by impact and uncertainty categories, the quality attributes were categorized by CQA classification and summarized in Table 1. Nine analytical methods were used for the similarity assessment of SB3. Among them, five quality attributes met the criteria (RPN > 24) for CQA, in which Fab-related biological activities were included as the main MoA of trastuzumab. The effector-function–related attributes, especially ADCC and FcγRIIIa binding directly related to the MoA of trastuzumab, and FcRn binding that may affect the half-life were also categorized as a CQA.
Quality attributes and analytical method by CQA classification
Product quality attribute
RPN
CQA classification
Uncertaintyb
Fab-related biological activity
Anti-proliferation activity
Cell-based assay
HER2 binding activity
Fc-related biological activity
FcγRIIIa binding activity
AlphaScreen®
FcγRIa binding activity
Non-CQA
FcγRIIa binding activity
FcγRIIb binding activity
FcRn binding
C1q binding
ADCC antibody-dependent cell-mediated cytotoxicity, CQA critical quality attribute, ELISA enzyme-linked immunosorbent assay, FcRn neonatal Fc receptor, FRET fluorescence resonance energy transfer, HER2 human epidermal growth factor receptor 2, RPN risk priority number
aImpact was scored by 5 categorizations as very low, low, moderate, high, and very high
bUncertainty was scored by 4 categorizations as low, moderate, high, and very high
3.2 Determination of Quality Target for Biological Activity of SB3
A previously reported study demonstrated changes in the N-glycan profile, FcγRIIIa binding activity, and relative ADCC activity of EU- and US-sourced reference product [21]. The attributes for the N-glycan profile, FcγRIIIa binding activity, and relative ADCC activity showed two marked changes throughout the monitoring period. In the first instance, %galactose and %afucose were decreased. Hereafter, the level of %high mannose was remarkably elevated, which was defined as the second instance. Since N-glycan levels correlate with relative ADCC activity and FcγRIIIa binding activity is associated with effector binding in the Fc region during ADCC [22], the change in the N-glycan profile resulted in a downward shift of ADCC and FcγRIIIa binding activities in the reference product. Since publishing the data by Kim et al. [21], we have kept monitoring the biological profile trend of the reference product. In recent lots (having an expiry date after February 2020), the biological profile of the reference product recovered to a status similar to that of pre-changed lots (Fig. 1). Therefore, it seems that the first and second changes in biological profile in certain periods were abnormal events; considering that ADCC is a major MoA, such changes in the biological profile have the potential to impact clinical efficacy of the reference product. Furthermore, in terms of similarity assessment, this change in the biological profile of the reference product brings about product variability and can affect the consistency of the target similarity range [mean ± 3SD(standard deviation)], as shown especially in Fc-related attributes (Fig. 2).
Trends of Fc-related biological attributes of the reference product. Dotted line shows the min–max range of expiry date before August 2018, 1st alteration, 2nd alteration, and post-alteration. a %Afucose, b %high mannose, c %afucose + %high mannose, d %galactosylation (%G1F + %G2F), e ADCC activity, and f FcγRIIIa binding activity. ADCC antibody-dependent cell-mediated cytotoxicity, FcγR Fcγ receptor, G1F FA2[3]G1 or FA2[6]G1, G2F FA2G2, M5 Mannose5, Man5, M6 Mannose6, Man6
Change of target ranges depending on the biological profile change periods of reference product. Boxplots show the mean ± 3SD ranges of EU- and US-sourced reference product for pre-alteration, altered, and post periods. a ADCC activity, b FcγRIIIa binding activity, c anti-proliferation activity, and d HER2 binding activity. ADCC antibody-dependent cell-mediated cytotoxicity, HER2 human epidermal growth factor receptor 2, FcγR Fcγ receptor, SD standard deviation
Accordingly, in this study, the target quality ranges were established by excluding the lots displaying these altered biological profiles and exclusively using pre-change lots in order to appropriately compare SB3 to the reference product.
3.3 Fab-Related Biological Attributes
Based on the MoA of trastuzumab, two sets of biological assays were performed to evaluate the Fab-related activities: anti-proliferation assays and HER2 binding assays. Trastuzumab binds to the extracellular domain IV region of HER2, and blocks proteolytic cleavage of the extracellular domain of HER2, leading to downregulation of the MAPK and PI3K/Akt pathways and inhibition of cell proliferation. HER2 binding activity was determined by a FRET-based competitive inhibition binding assay, and the result showed that SB3 is similar to EU- and US-sourced reference product. The mean values of %relative binding activity for SB3 and EU- and US-sourced reference product were 100%, 99%, and 98%, respectively. In addition, HER2 binding activities of all SB3 batches were within the target similarity range set by mean ± 3SD, demonstrating promising similarity in HER2 binding activity (Fig. 3a). For the anti-proliferation assay, the CellTiter-Blue® kit was used to indicate cell viability in the HER2-overexpressing human breast cancer cell line BT474. The mean values of %relative anti-proliferation potency for SB3 and EU- and US-sourced reference product were 96%, 100%, and 100% respectively. All SB3 batches also showed relative potencies within the similarity range, demonstrating promising similarity in anti-proliferation potency (Fig. 3b). Therefore, these results indicate that SB3 is evidently similar to the reference product in terms of Fab-related biological attributes.
Comparison of the Fab-related biological activities of SB3 and reference product. Dotted line shows the similarity range (mean ± 3SD) of pre-altered EU-sourced reference product. Solid line shows the mean ± 3SD range including pre-altered and altered EU-sourced reference product. a HER2 binding activity and b anti-proliferation activity. HER2 human epidermal growth factor receptor 2, SD standard deviation
3.4 Fc-Related Biological Attributes
The Fc region of trastuzumab binds to FcγRs, FcRn, and C1q (a complement protein) for most of its effector functions and in vivo stability [23]. The interaction of the Fc region in the target-bound antibody with FcγRIIIa (a member of FcγRs) on the effector cell is the key mechanism of ADCC for trastuzumab [24, 25, 26]. As CQAs of Fc-related biological attributes, ADCC, FcγRIIIa binding, and FcRn binding activities were assessed to demonstrate the similarity of SB3. The mean values of relative ADCC potency for SB3 and EU- and US-sourced reference product were 98%, 85%, and 89%, respectively, and those of relative FcγRIIIa binding activities were 98%, 84%, and 88%, respectively. These mean differences for ADCC and FcγRIIIa binding activities are considered to result from the reference products with altered biological profiles. To verify this hypothesis, the similarity of SB3 was re-assessed with only the mean values and the similarity ranges excluding the reference products with altered biological profiles. As a result, the mean value of SB3 was similar to the quality of pre-altered reference products, and all data for independent batches fell within the tightened target similarity range (Fig. 4).
Comparison of the Fc-related biological activities of SB3 and reference product. Dotted line shows the similarity range (mean ± 3SD) of pre-altered EU-sourced reference product. Solid line shows the mean ± 3SD range including pre-altered and altered EU-sourced reference product. a ADCC activity, b FcγRIIIa binding activity, and c FcRn binding activity. ADCC antibody-dependent cell-mediated cytotoxicity, FcγR Fcγ receptor, FcRn neonatal Fc receptor, SD standard deviation
Affinity binding to FcRn is critical to extend the half-life of mAb by recycling and exocytosis at the plasma membrane [27]. The mean values of relative FcRn binding activity for SB3 and EU- and US-sourced reference product were 96%, 88%, and 93%, respectively (Fig. 4). Furthermore, all SB3 batches were within the similarity range, demonstrating similarity in FcRn binding activity.
Binding activities for other FcγRs (FcγRIa, FcγRIIa, and FcγRIIb) were also tested as part of the similarity assessment. All FcγRs belong to the immunoglobulin superfamily and are the most important Fc receptors for inducing phagocytosis of microbes. This superfamily includes several members such as FcγRI (CD64), FcγRII (CD32), and FcγRIII (CD16), which differ in their affinities for antibodies and in their functions [28]. In the case of trastuzumab, ADCC would be affected by FcγRIIIa rather than FcγRIa, FcγRIIa, and FcγRIIb [29]. Therefore, the other FcγRs were categorized as non-CQA even though they should be controlled within the range to demonstrate biosimilarity. The mean values of relative binding activities for other FcγRs of SB3 were similar to reference product, summarized in Fig. 5, including the similarity ranges. In the same manner, SB3 demonstrated similarity to the reference product for C1q binding activity that induces complement-dependent cytotoxicity (CDC) (Fig. 5).
Binding activities for FcγRs and C1q of SB3 and reference product. Dotted line shows the similarity range (mean ± 3SD) of pre-altered EU-sourced reference product. Solid line shows the mean ± 3SD range including pre-altered and altered EU-sourced reference product. a FcγRIa binding activity, b FcγRIIa binding activity, c FcγRIIb binding activity, and d C1q binding activity. FcγR Fcγ receptor, SD standard deviation
Taken together, in all the SB3 batches tested, each of the Fc-related biological activities fell within the similarity range. These data strongly support the similarity of SB3 to the reference product in Fc-related as well as Fab-related attributes.
Extensive analytical characterization is a key component for demonstrating similarity of a proposed therapeutic protein product as a biosimilar to a reference product. To understand the biological quality attributes of trastuzumab, we characterized up to 154 lots of EU- and US-sourced reference product and established reliable similarity acceptance criteria. Based on information obtained about these attributes, SB3 was developed as a trastuzumab biosimilar and approved by the EC as the first trastuzumab biosimilar in the EU. Although the analytical similarity of SB3 was assessed with quality attributes covering a wide spectrum of structural/physicochemical and functional characteristics, this study only includes functional characteristics. Briefly, the majority of biological attributes categorized as CQAs met established similarity acceptance criteria. SB3 was similar to both EU- and US-sourced reference product in Fab-related functional activities, including HER2 binding and anti-proliferation. The similarity of SB3 was also demonstrated in Fc-related attributes including ADCC, FcγRIIIa binding and FcRn binding activities. Additionally, other FcγR binding activities conformed to the similarity range set by the reference products.
ADCC is an important MoA of trastuzumab and is significantly correlated with the level of the sum of afucosylated glycan and high mannose, as well as FcγRIIIa binding activity [7]. By binding of the Fc part of IgG to FcγRIIIa (CD16) expressed on natural killer cells, target cell-bound mAbs induce ADCC. Since the affinity of FcγRs to the Fc part is influenced by N-glycosylation, ADCC is enhanced for mAbs with lower fucosylation. The glycosylation pattern has inherent variation from one batch to another, but can also be changed in manufacturing processes [30]. Among the various features of N-glycans, the levels of the afucosyl and high-mannose forms (labeled %afucose and %high mannose, respectively) correlate with ADCC and FcγRIIIa binding activities, and the level of galactosylation correlates with CDC and C1q binding activities. As discussed in Kim et al., fluctuations were observed in biological attributes including %afucose + %high mannose, FcγRIIIa binding, and ADCC in certain lots of reference products. In addition, %galactosylation was also altered, which might affect C1q binding and CDC activities. However, the C1q binding activity of the reference product was not altered during that period, which indicated that the influence of %galactosylation change is not enough to affect functional activity [21]. Incorporating these fluctuations in setting the quality targets for a similarity assessment could result in broader similarity acceptance criteria. Therefore, the data from these lots displaying changed biological profiles were excluded from establishing the similarity acceptance criteria, resulting in more conservative target quality ranges for SB3. Even with the narrower quality target, the results indicated that SB3 is highly similar to the reference product in the respective Fc-related quality attributes including %afucose + %high mannose, ADCC, and FcγRIIIa binding activity (Figure 5).
Based on the reference product, the recent lots showed biological profile at the pre-change level, which means that even though the cause of the biological profile change is still unknown, the change in biological profiles was transient. The abrupt changes in biological profile also occurred in other marketed products, Rituxan® and Enbrel®, which showed alterations of N-glycan and ADCC activity as well as the reference product. According to the literature, these observed biological profile changes in the products might be caused by changes in the manufacturing processes such as cell production, growth conditions, and purification sequence [30]. However, in terms of the relevance to clinical efficacy, the influence of these alterations in biological profiles in product lots cannot be confirmed without additional clinical studies. Nevertheless, it is critical for assessing the similarity of a biosimilar product that the quality target is established without any meaningful difference from the originally approved molecular entity. As in the case of SB3, any incidental changes in the biological profile of a reference product could become a hurdle with regard to establishing the appropriate quality target, with the potential for a clinically meaningful difference in a developed biosimilar.
In conclusion, SB3 is deemed to show similar efficacy and safety to the reference product in proven indications.
We would like to thank Kyung-Ah Kim for internal review and proofreading of the manuscript.
Compliance with Ethical Standards
This work was funded by Samsung Bioepis Co., Ltd.
The authors, Jae Hee Lee, Kyungyeol Paek, Jae Hyon Moon, Sunyoung Ham, Jinsu Song, and Seokkyun Kim, are employees of Samsung Bioepis, and declare that they have no conflict of interest.
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Open AccessThis article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.org/licenses/by-nc/4.0/), which permits any noncommercial use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
1.Quality Evaluation Team, Samsung Bioepis Co., LtdIncheonRepublic of Korea
Lee, J.H., Paek, K., Moon, J.H. et al. BioDrugs (2019). https://doi.org/10.1007/s40259-019-00362-5
First Online 12 June 2019


Forbes Regional & Allegheny Valley Hospitals from Glenn Przyborski on Vimeo.
Over the years, I've directed and photographed literally hundreds of TV spots for medical centers across the country. This multi-hospital campaign featured similar commercials for Forbes Regional, Allegheny Valley & Canonsburg General Hospital.
Rather than using professional actors and voice-over talent, the campaign's concept required a real doctor at each facility to talk one-on-one about the services his hospital offers to the community it serves.
Our challenge was a very tight, one day production schedule at each hospital with a limited time to shoot the on-camera doctors. Fortunately, I've had years of experience shooting, directing and working with non-professional on-camera talent.
We broke the scripts down to minimize each doctor's on-camera segments. You can overwhelm "talent" if you ask them to memorize a long, complicated script. The doctors were told that they never had to deliver more than 2 on-camera sentences in each sequence. We didn't waste time shooting copy that was intended to be covered with "B-Roll".


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Mon, 28 September 2020
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