In April, SAFC Live highlighted Patty Benson’s participation at the ICH Q3D Metal Impurities Workshop in Bethesda, Maryland as part of a panel presentation where she provided an API supplier’s perspective. As a follow up to that piece, we sat down with Patty to discuss the Bulk Pharmaceutical Task Force (BPTF) in more detail. Here, she offers insight into who the BPTF is, what they do, what they are currently working on and what the future holds. The full story follows:
Over the past five years, a great spotlight has been placed on regulatory standards in the Pharma industry. Landmark scandals, such as the heparin scare of 2008, have forced the industry to come together to find innovative ways to source and manufacture safer products, while also increasing speed to market and security of supply chain. It is not an individual company or country issue, but rather a worldwide Pharma industry issue, and often times the lack of standardization of regulations across the industry creates setbacks. End user (patient) health has to remain top of mind and in order to be successful, companies need to be absolutely certain that the ingredients that they source come from reliable and secure places.
While some countries are ahead of the curve in regulations, others are still coming up to speed, and it is important to find ways to level the playing field for global companies. The Bulk Pharmaceutical Task Force (BPTF) recognizes this as an issue and is working with their members, and the greater pharmaceutical and regulatory communities, to find ways to ensure that the US drug supply chain is secure and that patients are protected.
As a member and chair of the Bulk Pharmaceutical Task Force, SAFC’s Director of Quality Assurance, Patty Benson has insight into the mission of group, as well as the future of the API industry. Here, Patty took the time to sit down and discuss a few of these items with SAFC Live.
Thank you for joining us, Patty. Please start by explaining what the Bulk Pharmaceutical Task Force is.
It is an affiliate organization of SOCMA (the US Society of Chemical Manufacturers and Affiliates) and it represents companies who manufacture or sell APIs, excipients and advanced intermediates into the US market. As these are FDA-regulated products, we have a lot of dealings with the US FDA and also the European counterparts. While some of the member companies may have headquarters in Europe, all do business in the US.
What benefits does it offer its members?
Perhaps the most important benefit is that we continuously review the legislation and guidance that comes out of various countries. Most of these legislation and guidance documents have a commenting process where input is requested from the industry and other stakeholders. The documents are often revised to take the industry comments into account. BPTF stays current on the documents and represents its members in providing these comments.
In recent years, for example, we have commented on chapters of the US Pharmacopeia regarding residual solvents and heavy metals. We have also commented on guidance documents, such as the recent European guidance on GMP for API manufacturers. We are able to provide a mechanism for member organizations to combine their thoughts and their comments, and give a single response that, hopefully, will carry more weight.
What about links to the regulators? Do you engage with them on behalf of members?
Yes, we do. A good example of this is the proposed Generic Drug User Fee Act, or GDUFA. It is similar to PDUFA for prescription medicines, and would allow the FDA to collect fees from generic product and API manufacturers to help fund application reviews and inspections. At present, there is a huge backlog of generic applications in the US which is largely due to the time involved for approvals; on average it can take about 30 months for a generic application to be approved. That is way too long. So the FDA approached us, along with the European Fine Chemicals Group in Europe (an organization in Europe that is affiliated with European chemicals trade association Cefic) and the Generic Pharmaceuticals Association (trade organization for generic drug manufacturers), to work together to develop GDUFA which is now in the process of becoming law.
Are there any other big issues that BPTF is concerned about?
One important issue we have become concerned with in recent years is the lack of parity between US, European and Japanese manufacturers, and those from countries like China and India, where regulations are more lax. The US FDA has a regulatory obligation to inspect US manufacturers every two years, yet there is no such regulatory requirement for foreign manufacturers. This presents a very uneven playing field to US manufacturers – especially as foreign manufacturers supply about 80% of all the APIs that are used in the US. We have put forward citizens’ petitions on this, and one of the primary focuses of the GDUFA negotiations was trying to bring inspection parity between foreign manufacturers and those based in the US. We also recognize that other heavily regulated markets like Europe, Japan, Australia and Canada have similar regulatory requirements to those in the US, so we believe that the FDA should focus its limited resources on those countries where the regulatory pathway is not as mature. The whole reason for looking at the quality of ingredients is to minimize patient risk, and there is certainly not as much patient risk from ingredients originating in highly regulated countries as from those where the regulatory system is less mature. Yet there is still a lack of parity with EU manufacturers – if they are inspected by the FDA they will be notified in advance and the duration of the inspection is usually limited; this is true of any foreign country inspection. This is in contrast to the US, where the inspectors arrive unannounced, and the inspection can last much longer. Our ultimate goal is to achieve parity between inspections in the US and those carried out in any foreign country.
What other benefits does it offer SAFC as a company?
In my personal opinion, one of the major benefits is being able to network with other people in the same business. Certainly, we have to work under strict antitrust guidelines, and of course we do not speak about topics such as pricing or customers, but it does allow us to bounce questions off people who have similar experiences, and may have faced a similar issue before. We generally have a very good relationship with the people we meet within BPTF, and use this to develop and share best practices in terms of how to manufacture APIs, excipients and advanced intermediates. I believe this is a real benefit to the patients we are ultimately serving.
Does BPTF do anything else?
In the past it has sponsored courses, particularly GMP courses, to train people within the industry by bringing in regulatory experts, including FDA representatives. This has not been done for a little while, partly due to economic reasons and restricted travel budgets, but we are now looking at what other education tools we can offer, such as webinars. We also have published best practices and guidance for members to reference, such as the quality agreement template that drug product manufacturers can use to help them set up quality agreements with their API manufacturers. It takes into account the regulations, what API manufacturers are expected to do, and the kind of information they have to communicate back to the drug product manufacturers. Then when customers use this template, the API manufacturers do not have to deal with quality agreements in varying formats, which makes managing quality much more straightforward.
Another activity is our work with the International Pharmaceutical Excipients Council, where we have partnered on some of the issues in the heavy metals guidance that ICH is working on. Finally, we also work with Rx-360, the international supply chain consortium, where we have observer status, and SAFC is a board member.
So what issues are in the pipeline for the near future?
The ICH is reworking heavy metals guidance with the expectation that both the US Pharmacopeia and the European Pharmacopeia will follow what ICH develops. That will then get both agencies, plus the various other regulatory agencies, working together on how exactly to implement heavy metals testing.
Another item on the horizon, of course, is GDUFA; these regulations are now working their way through the legislature. Though we do not know exactly what it will look like once Congress is finished with it or how the FDA will implement it, it is something we await with much interest.