QbD Pioneer Afnan to Leave FDA

One of the true thought leaders behind pharma's PAT and Quality by Design movement, Ali Afnan, PhD, has decided to leave his post at FDA. In today's On Pharma blog, Agnes Shanley looks back at Afnan's key role within FDA, and muses about his reasons for moving on.

Tufts Center: Approval Times Have Dropped, But Is It Enough?

For those of us who work in and follow the drug industry, winter is always made a bit brighter and warmer with the coming of the annual Outlook paper by the Tufts Center for the Study of Drug Development. The Tufts report is one of the definitive measures of where we are, where we're heading, and what hoops we have to jump through to get there.

This year's report (here's the Center's summary; the full Outlook 2010 will be made available to non-subscribers this spring) has plenty to chew on, but here are a few of the more relevant points that drug developers and QbD professionals need to consider:

--Few drugs make it to market, but it's important to remember that of those that do, only 3 of 10 generate enough revenue to sustain R&D.
--Drug developers don't just need to improve time to market, they need to dramatically change what they're doing--to "transform the way they conduct research and development over the medium and longer term to be more efficient and productive."
--Collaboration is critical. R&D success will depend upon how developers engage their partners at critical points in the product lifecycle.
--Risk management will continue to balloon in importance. With FDA and global regulators limited in their resources, it will be left up to developers to show expertise via Risk Evaluation and Mitigation Strategies (REMS)
--Biotech products will boom, but take longer to get to market due to increased clincial trial requirements.

Just a few thoughts to warm your winter.

Where Lies QbD's Competitive Advantage?

I've had the good fortune of speaking this week with Volker Eck, senior director of science and technology at PDA, and a day later with Graham Cook, Wyeth's senior director for process knowledge/Quality by Design. Both men were integral participants in late September's workshop in Frankfurt,  hosted by PDA, to unveil and discuss EFPIA's mock examples of Quality by Design implementation.

By all accounts, the mock examples were well received and the meeting was an important step toward helping manufacturers not just interpret ICH guidances but grasp how QbD might look for their products and processes. The mock examples are now being finalized, following input from the Frankfurt meeting and one earlier with EMEA in London, and are expected to be made public later this year.

You can read my summary of Eck's take on the meeting here, and I hope to have a podcast of my interview with Cook available within a week or two. Eck was insightful in that he said that many manufacturers at the Frankfurt meeting were still clearly struggling to "translate" the ICH documents, and the mock examples, to their own operations. With QbD, manufacturers can only truly learn by doing and thus will have to dive in

What Lessons Will We Take Away from H1N1 Vaccine Development and Approvals?

Cutting Edge Information specializes in paid research reports for pharmaceutical decisionmakers, but yesterday sent out a press release not plugging a new report but simply opining on what lessons will be learned from the rapid and, it appears, successful development of new vaccines to tackle the swine flu pandemic. And what's to be gleaned from how quickly these drugs were approved by global regulators?

CEI raises some salient issues: if H1N1 vaccines can be successfully fast-tracked, shouldn't this open the door for more rapid and favorable regulatory review of oncology drugs and other products that clearly

FDA Initiates Study of QbD for Lyo Protein Product Manufacturing

FDA has released a synopsis of a project to study the development of QbD for lyophilized protein parenteral manufacturing. The parties involved in the one-year project include Baxter Pharmaceutical Solutions, Purdue University, University of Iowa, and University of Connecticut.

--Paul Thomas

FDA, EMEA Harmonize Around Clinical Practices

FDA and EMEA announced today a broad collaborative effort in the area of Good Clinical Practices. The joint effort bodes well for continued cooperation between the agencies on many fronts, and in the sharing of resources that is imperative if global regulatory authorities are to get the most out of their limited resources. The agreement also represents a significant step toward the agencies' recognizing each other's inspections as valid and binding, and toward reducing the regulatory burden upon drug companies who operate trials worldwide and must satisfy the requirements of multiple regulatory authorities.

--Paul Thomas

ADAPT Agenda Set; Throckmorton to Speak

The final agenda is available for September's ADAPT (Accelerating Development and Advancing Personalized Therapy) congress in Washington, D.C.

A quick summary of the tracks:

Track 1: Optimizing Clinical Trials
Track 2: Implementing Personalized Medicine
Track 3: Advancing Cancer Therapy
Track 4: Bridging Silos in Biomarker Development

Featured speakers include FDA Deputy Director Douglas Throckmorton; J. Carl Barrett, VP, Global Head Oncology Translational
Medicine, Novartis; Nicholas C. Dracopoli, VP, Biomarkers, Centocor R&D, Johnson & Johnson; and Giora Feuerstein, AVP, Head,Discovery Translational Medicine, Wyeth Research.

--Paul Thomas

QbD for Biopharma: New Course at PDA FDA Joint Conference

This year's PDA FDA Joint Regulatory Conference in D.C. in mid-September has an excellent program top to bottom. (Here's the agenda.) It will also feature a new course by Anurag Rathore (see yesterday's post on his new book) on QbD for Biopharma.

Rathore has just posted the tentative outline for the course on our LinkedIn group. If you're not a LinkedIn member, here is his overview--comments are welcome as the program is finalized.

Critical Quality Attributes (Patrick Swann): Potential CQAs for Mabs; Biological Activity Matrix; Product-related variants; Characterization of variants and setting limits (ICH Q5E); Clinical pharmacology studies; Specifications (ICH Q6B); Biological characterization

Design Space (Anurag Rathore): Clinical design space; Product design space; Process design space; Case Study I – Establishing process design space for a Pichia fermentation product; Scale down modeling; Failure Mode and Effects Analysis (FMEA); Design of Experiments (DOE); Parameter-parameter interactions; Worst case studies

Group work I (All): Group discussion to identify and list gaps attendees see with respect to molecules under commercialization at present and also legacy products.

Risk Assessment and Management (Patrick Swann): Review of historical approaches; ICH Q9 guidance; Quality risk management process; FMEA

Regulatory Aspects (Patrick Swann): OBP QbD pilot program; Observations based on review of proposals for categorizing quality attributes

Establishing Control Strategy and Lifecycle Management of Design Space (Anurag Rathore): Creating control strategy; Process validation; Filing; Process monitoring; Raw material management; Process analytical technology (PAT); Case Stud II – Multivariate analysis for a mammalian cell culture step

Group work II (All): Group discussion of gaps identified earlier

H1N1 Puts Onus on Industry to Embrace QbD and FDA's Risk-based Dream

If ever there were a time for the industry to embrace QbD, it is now, as the threat of an expanding H1N1 pandemic looms and manufacturers scramble to develop and manufacture significant volumes of vaccines to counter the spread of the virus. In this his latest article (also published in the July/August issue of Pharmaceutical Manufacturing), Pharmatech's Bikash Chatterjee puts the threat in perspective (looking back towards the bird flu and even Spanish flu of 1918), and makes an impassioned case for the adoption of Q8 and Q9 principles as a means of accelerating development and helping to reduce or even extinguish the danger that H1N1 presents.

He concludes:

For an industry that has had its fair share of bad press in the last few years over public safety concerns, this is our chance to step up to the plate and show we can deliver when we need to. If we fail, the FDA can look to another long, slow transition as it struggles to enforce its new policies on risk-based process development and quality assurance.

--Paul Thomas

Risk Management Strategies for Extractables and Leachables

FDA's Ingrid Markovic has just published in American Pharmaceutical Review on risk management for extractables and leachables. Here's a link (subscription required), and here is the abstract:

Extractables and leachables (E&L) are chemical entities, which can be released into intermediate material or final therapeutic biologic protein product at various times during upstream and/ or downstream manufacturing steps, packaging operations and/or storage. These substances may pose a safety risk to the patient by causing toxicity, carcinogenicity, immunogenicity and/or endocrine dysregulation. They may also alter product physico-chemical properties via direct interaction with the active pharmaceutical ingredient or, indirectly, by interacting with the excipients in product vehicle, thereby adversely affecting the product quality. Current paper will address a risk-based approach to conceptualizing, evaluating and executing identification and characterization of E&L along with regulatory considerations regarding the impact of these impurities on product quality, patient safety and clinical efficacy. Selected case studies are presented and discussed.

On the Horizon: Drug Discovery and Development Week

Drug Discovery and Development Week, a collection of five conference themes around one exhibition, is slated for the first week of August in Boston. Among the highlights: In the Drug Safety Strategies to De-Risk Compounds event, William Mattes, former director of toxicology for the Critical Path Institute, will deliver a keynote on Skirting Drug Safety Potholes in the Critical Path to POC, while FDA senior scientific advisor Wendy Sanhai will discuss Biomarker Development and Clinical Qualification. The Cancer Drug Development track will feature a debate on the effectiveness of current methods of development via cancer stem cells. There's plenty more on hand, of course, including a keynote by Daiichi Sankyo president and CEO Takashi Shoda, on the challenges of building a global drug company in today's market.

--Paul Thomas

Forbes: Scale is the Real Reason for Big Pharma Mergers

Interesting article from Forbes, which posits that the real reason that big pharma companies are merging is not to shore up their weak pipelines, but to increase their scale in order to increase the likelihood of bringing more products to market, faster, and in more parts of the world. No longer is approval by the U.S. FDA the preeminent goal for any drug, but rather getting approved in many markets as quickly as possible.

--Paul Thomas