Could Ben Venue’s Manufacturing Suspension Have Been Avoided?
When only a handful of manufacturers supply a given drug, production problems at any of those companies can lead to a shortage. Earlier this year, problems at Ben Venue’s Bedford, Ohio, site contributed to shortages of the cancer drug Doxil. The shortages are likely to continue now that Ben Venue has suspended manufacturing at the plant.
After reviewing its documentation, the company concluded that routine preventive maintenance and requalification of manufacturing equipment at the site was overdue. Ben Venue suspended manufacturing so that it could assess the entire site and take appropriate corrective actions to ensure the safety of its products. The suspension will affect Johnson & Johnson, which markets Doxil, as well as Pfizer, Hospira, and Teva.
Last month, President Obama ordered FDA to take various steps intended to prevent and reduce drug shortages. The agency will require advance notice from manufacturers likely to face manufacturing disruptions, and it will expedite reviews of new drug suppliers, production sites, and manufacturing changes.
These steps, while helpful, do not address an important factor that contributes to drug shortages: manufacturing deficiencies. Even before Ben Venue conducted its own review, FDA found 48 quality concerns during an inspection of the Bedford site in May 2011. FDA likely needs a larger pool of inspectors to oversee drug manufacturing sites more thoroughly. But the government’s current desire for austerity will probably preclude the budget increase that would make hiring possible.
Maybe FDA should prioritize manufacturing sites for inspection if they are among a few that produce a medically necessary drug such as Doxil. Greater attention to crucial sites could identify problems earlier and, ideally, resolve them without disrupting drug supply.
Or, perhaps, there needs to be some sort of back up system — more than one manufacturing line– for such important drugs.
What it is as clear as water is that Doxil / Caelix shortage could have been easily avoided. It is a nonsense to have only one contract manufacturer the the worldwide supply of an anticancer drug. A medal for J&J!!!!
I imagine that the comments from affected oncologic patients and their families will be sharper.
This company has been so poorly run for so long and so many short cuts were taken it is amazing they havent locked the doors.
Everyone who is anyone, in both the agency and industry knows that the manufacturing issues at BVL are nothing new. They have been a necessary evil for several decades due to: 1) their willingness to manufacture small-scale batches of Investigational drug that other organizations either wouldn’t or couldn’t handle – to include NCI clinical trial material and 2) the fact that the outsourcing deals which have historically been signed have been solely based on pricing – quality and compliance have been an afterthought. How many people out there are willing to stop a moving train?
What seems to be forgotten in all this is that the organisations that should be accountable for this mess are the Contract Givers. Yes Ben Venue need to get their house in order, BUT the Agencies (US/EU/Japan etc) should be coming down like the proverbial ton of bricks on the quality unit heads and QPs responsible for releasing the product to the market when there has clearly been ineffective supervision of the contractor by the holders of the product licences.
Contract Acceptors always have different objectives to Contract Givers and it is the clear responsibility of the Contact Givers to keep them on the straight and narrow. It is totally wrong in my opinion for the Industry to rely on the Regulatory Agencies to oversee supply chains for them. Agencies don’t have the resources to do that. The Quality Managers need to have the authority and indeed the courage to say “NO” when they see violations (and STOP that moving train!).
Indeed, the contract giver should undertake appropriate diligence assessments as a key part of their choice of supplier. Was this a rigorous assessment, market forces would soon dictate that poor quality suppliers would be out of business. However, it is clear to see that the focus on cost reduction as No1 business goal is affecting all aspects of the pharma supply chain, from R&D all the way through to commercial supply.
It is ironic that so much is said about the costs of drug development being so high, and yet companies still seem to take a “gung-ho” attitude to securing their supply chains when they have finally succeeded in getting a compound to late development or market.
That being said – a Western-based CMO competing in a highly competitive global market SHOULD have quality at the top of its agenda.
First, Eric G should better educate himself on the industry! The FDA has a risk based priority program in place. Sterile injectables, regardless of the other factors in the evaluation, are THE number one priority in the pharma industry. A question that could be asked is…does the FDA have ‘enough’ qualified sterile injectable inspectors to do the job. I think the answer is obviously NO.
BenVenue is not unlike other manufacturers in that senior management over the last 30 plus years has NOT learned anything about compliance. There is no argument that can possibly hold water when you look at the number of regulatory actions over the years. From Abbott’s consent decree & fine to the consent decrees/fines and severe warnings letters today, very little attention is being paid to compliance issues. Decisions are risk based…how likely is it that the FDA will find the problems and or shut us down…that is senior managements thinking. Prevention is NOT in their vocabulary! Look at J&J, there senoir management was MORE concerned with their stocks holders’ suit against them for failing to do their jobs (which a blindman could see they had been a complete failure in performing/meeting their responsibilities) than they were with ‘fixing’ any problems (by the way, they had been working with, or playing with as the case may be, for 2-4 years. What does it take to convince senior management they have problems/issues?? Pick on or at BenVenue if you like, but you certainly lack the industry knowledge/experience to know that this is an INDUSTRY problem, not a one or two company issue.
Thanks to everyone who commented on this post. It certainly generated more interest than I expected. I agree with Carey and Joseph that the ideal situation would be to have backup production lines and more than one provider for any necessary drug.
Ryan and Jeff are right to point out that Ben Venue has had problems for some time. Witness the company’s decisions to exit the contract-manufacturing business and suspend manufacturing in Bedford.
Thanks to Chris for pointing out sponsor companies’ responsibility to oversee their contractors. I think that regulatory agencies ideally should play the biggest role in overseeing contractors, but their lack of funds makes it important for sponsors to step up to the plate.
Buckshot is right when he says that quality and compliance problems are not unique to one company. J&J and Abbott are fine examples to adduce.
He is not right, though, when he says that I don’t know that the entire industry has problems with quality and compliance. I direct him to my previous posts about Genzyme, McNeil, and Ranbaxy. I did not write about Ben Venue to imply that it was a lone bad apple in the industry, but because the company was in the news, having just suspended manufacturing at its Bedford plant.
As a side note, I have written about FDA’s risk-based priority program, which Buckshot mentions, and I also have bemoaned FDA’s lack of inspectors and funds on many occasions.
Thanks again for all the comments. They show that our blog is provoking thought and debate, which is what we hope to do.
It’s hard to beleive that in this day and age, a Pharmaceutical Company like Borg.-Inger. (parent Co. of BenVenueLabs.) could allow this to happen. Even though they may manufacturer small pilot plant batches of important medications, this to me would’ve been a lot easier to control quality, cleaness, etc. Has Ben Venue Labs been completely shut down, or just certain areas of production. If the entire facility in Bedford, OH. is now closed, will it be re-opening soon?