Jill Wechsler is Pharmaceutical Technology's Washington Editor, jillwechsler7@gmail.com.

Jill Wechsler

	The continued surge in research and development of cell and gene therapies is prompting FDA officials to ramp up guidance development, streamline oversight, and take steps to advance manufacturing and clinical development of these cutting-edge treatments. This wave of innovation includes somatic cell gene therapies able to correct gene defects by replacing, repairing, or inactivating a gene, either by directly administered gene therapy to the patient or by taking cells from the body, modifying them in culture, and returning them to the patient.

	FDA’s Center for Biologics Evaluation and Research (CBER) has seen an “explosion” of growth in the cellular and gene therapy area, observed CBER Deputy Director Celia Witten at the 

 in June 2019 sponsored by CASSS (1). CBER’s Office of Tissues and Advanced Therapies (OTAT) received more than 400 investigational new drug applications (INDs) in 2018, many qualifying for breakthrough therapy status and the Regenerative Medicine Advanced Therapies (RMATs) designation for products that provide evidence of intent to treat, modify, or cure a serious or life-threatening disease or condition. For such therapies, FDA offers manufacturers extra assistance in developing innovative product testing and production methods, expedited review, and flexibility in documenting quality and meeting requirements.

	A main FDA challenge is to devise standards for this burgeoning cadre of experimental products. FDA is working with the National Institute for Standards and Technology (NIST) and has contracted with the Nexight Group to coordinate 

the standard development and assessment process

 (2). Collaborations seek standard practices in cell counting, measuring flow cytometry, and assuring cell viability. FDA also is engaged in devising common regulatory approaches and policies for developing and testing innovative therapies with authorities in other regions. The Gene Therapy Working Group of the International Pharmaceutical Regulators Programme (IPRP) has finalized a reflection paper on expectations for biodistribution assessments for gene therapy products (3). This may provide a basis for the International Council for Harmonization (ICH) to 

develop a guideline on biodistribution studies of gene therapy vectors 

	A main challenge in testing and developing these new therapies, Witten noted, is to devise new tools and policies to support more complex manufacturing processes. A lack of capacity for producing lentiviral and adeno-associated virus (AAV) vectors can limit clinical development, she observed, while current cell lines often are not able to meet demand for large-scale or rapid production. Regulators and sponsors are looking to advanced manufacturing technology devised for vaccine production processes to inform similar approaches for optimizing cell lines for production, improving yield of recombinant technology, and applying continuous manufacturing concepts to new treatments.

	The expedited development and approval of cellular and gene therapies requires a “new paradigm,” said Steven Oh, deputy director of OTAT’s Division of Cellular and Gene Therapies, at the CASSS symposium. He noted the unique challenges created by limited manufacturing experience prior to licensure and limited understanding of critical quality attributes (CQAs) due to difficulties in characterizing the drug product, drug substance, and in-process material for these therapies. Products vary, moreover, due to unusual source materials, less qualified assays, and limited stability data.

	Despite these difficulties, Oh emphasized that sponsors cannot ignore requirements for complying with chemistry, manufacturing, and controls (CMC) and current good manufacturing practice (cGMP) standards. It is important, therefore, to focus on these issues early in clinical development to support the accelerated review and approval of a product with a breakthrough or RMAT designation. Manufacturers should plan for commercial-scale manufacturing and conduct needed comparability studies as early as Phase I and II studies. Raw material qualification and supply chain issues should be addressed, and assays should be developed and validated.

	At the same time, FDA may exercise some flexibility on the type and extent of manufacturing information expected with a submission, particularly for validation strategies and the manufacturing scale-up program, Oh said. He added that such leeway will depend on product characteristics, the seriousness of the condition being treated, the type of manufacturing process, the robustness of a quality system, and the strength of the risk-based quality assessment. Regulatory flexibility usually will be linked to agreements on post-marketing commitments and requirements.

	To assist manufacturers in designing untraditional production or development programs, CBER officials have established the CBER 

 (CATT) to discuss and respond to queries from industry on advanced manufacturing and testing technologies (5). This team aims to assist in developing products where CBER has “limited experience with the manufacturing or development process.” CBER wants inquiries to briefly describe the technology, why it is novel and unique, its potential impact on product quality, and a summary of the manufacturing or development plan.

	Developers of innovative therapies similarly can use CBER’s INTERACT program (INitial Targeted Engagement for Regulatory Advice on CBER producTs). This replaces pre-pre-IND interactions and offers early-stage informal consultation on product development. INTERACT is particularly useful for complex or novel manufacturing technologies, innovative devices, and cutting-edge testing methodologies. Such early discussion provides nonbinding advice and doesn’t replace the recommended pre-IND meeting for products further along the development pathway.

	A CBER internal working group on advanced manufacturing is soliciting proposals to support innovation relevant to producing complex biologics, including novel and improved materials, manufacturing innovations, and new analytical methods. CBER is expanding laboratory research programs and collaborating with academics and other partners to develop improved cell lines for vector production and advanced manufacturing technologies.

	These strategies to provide appropriate and efficient pathways for bringing innovative therapies to patients so far have involved treatments for single-gene disorders that generally affect very small patient populations. The challenges will increase as more manufacturers propose remedies for multigenic targets, such as Parkinson’s disease, which will involve new approaches for clinical trials and for production scale-up.

FDA’s Approach to the Development of Cell and Gene Therapy Products

,” presentation at Cell & Gene Therapy Products Symposium 2019, June 10, 2019. 

	2. FDA, Standards Development for Regenerative Medicines Therapies,

International Pharmaceutical Regulations Programme

Significant Advancements in Global Harmonisation Efforts at ICH’s Largest Biannual Meeting to Date

	5. FDA, CBER Advanced Technologies Team, 


	Vol. 43, No. 8
	August 2019
	Pages: 14-15

	When referring to this article, please cite it as J. Wechsler, "FDA Maps Strategies to Advance Cell and Gene Therapies," 

Articles

New tools and policies aim to support more complex manufacturing processes.

FDA Maps Strategies to Advance Cell and Gene Therapies

	In a notable about-face, the Trump Administration announced new policies to facilitate access to cheaper drugs from Canada and other countries for US patients. Democrats in Congress have promoted such action as part of more extensive legislation to limit outlays on medicines, but wider drug importing generally has been opposed by Republicans, as well as the Department of Health and Human Services and FDA officials, even in Democratic administrations.

	This time, however, easier access to drugs from other nations was trumpeted by Health and Human Services Secretary, Alex Azar, and supported by FDA Acting Administrator, Ned Sharpless. Previously, Azar had termed drug importation a “gimmick” that could not be done safely. Now the reformers consider more advanced drug tracking, labeling and import oversight systems able to ensure that products marketed outside the United States are of similar quality and efficacy as those distributed at home.

	However, the path to wider importing remains complex and lengthy, with analysts predicting that few if any drugs would reach US consumers under the new program before the 2020 election.

” proposes two pathways for obtaining drugs from foreign markets. Pathway 1 encourages states, wholesalers, or pharmacists to propose demonstration projects for importing drugs approved in Canada that are the same as those marketed in the US. However, the program excludes multiple important therapies, including biological products, infused or injected drugs, controlled substances, certain parenterals, and drugs inhaled during surgery, limiting its potential impact. To authorize such action, FDA would issue a Notice of Proposed Rulemaking (NPRM) to revise current rules governing section 804 of the Food, Drug & Cosmetic Act, a process that usually takes years to accomplish. The new rule would allow applicants to establish demonstration projects that meet requirements for importing compliant therapies.

	Under Pathway 2, pharmaceutical companies would be allowed to import approved drugs sold overseas under different national drug codes (NDCs), with assurance that the foreign version is the same as that marketed in the US. Imports could include expensive biologics such as insulin and cancer therapies and theoretically would appeal to manufacturers caught in costly US rebate programs that raise drug prices. FDA guidance is needed to implement the program, another lengthy regulatory process.

	The larger issue here is why any pharma marketer would bring cheaper versions of its own products to the US. Pharmaceutical Research and Manufacturers of America (PhRMA) strongly opposes the plan, maintaining that there’s “no way to guarantee the safety of drugs that come into the country from outside the US supply chain.” Industry noted that 

to wider exporting of their drug supply for fear of wider shortages and higher costs. The lobbyists are lining up to ensure opposition from Republican lawmakers to the import plan, while counting on inaction until the end of next year.

	This latest drug reform proposal appears to be one more effort by the White House to champion lower drug prices in the wake of previous failures. An earlier initiative to tackle drug rebates collapsed after budget analysts determined that the program would raise costs for consumers. Drug pricing policy changes are included in bipartisan legislation moving forward in the Senate and proposed in the House, but Congress won’t take any further action until this fall.

FDA, Health and Human Services, and the Trump Administration back cheaper foreign drugs to cut pharma costs. 

Drug Importing Back on Center Stage

	As part of its ongoing support for the development and approval of competitive biotech therapies, FDA has updated and clarified standards and procedures for ensuring the quality and similarity of biosimilars. A new draft guidance recommends a process for developing comparative analytical assessment plans to demonstrate biosimilarity, with added details on procedures for conducting such assessments and for documenting quality in a range of production lots to make biosimilar development and production more predictable and efficient (1).

	The new advisory replaces an earlier guidance on quality considerations for biosimilars issued in 2015 and updates a 2017 draft guidance on statistical approaches, both withdrawn later by FDA due to industry concerns and objections. This revised document presents strategies for conducting comparative analytical studies to assess biosimilarity to a reference product and for presenting scientific and technical information in the chemistry, manufacturing, and controls (CMC) section of biosimilar applications. There’s more detail on how comparative analytical assessments should cover key processes, including a product’s expression system, manufacturing process, physicochemical properties, functional activities, target binding, impurities, reference product and reference standards, finished drug product, and stability.

	To address concerns about lot-to-lot variability, FDA advises biosimilar makers to include data from at least 10 reference product lots acquired over several years to fully assess reference product drift. Similarly, sponsors should assess 6–10 lots of the proposed biosimilar, including both investigational and commercial-scale lots, validation lots, and lots manufactured at difference scales. Additional sections clarify the submission of reference standards and data on functional activity to demonstrate any structural differences with a reference product. And FDA provides the usual caveat that it will consider alternative approaches from sponsors in analyzing and presenting requested data. 

	FDA issued the revised quality assurance advisory soon after publication of a final guidance on developing interchangeable biosimilars, a much-anticipated and hotly debated option for manufacturers (2). That document updates a draft guidance from January 2017 that attracted voluminous comment from multiple stakeholders. The new version instructs manufacturers on conducting switching studies, which FDA says it usually will require to approve an interchangeable label. While some firms consider extensive switching studies unnecessary, FDA justifies this approach as important for demonstrating fully that safety and efficacy are not affected by changing treatment from brand to interchangeable, a finding that is considered important to gain the trust of physicians and patients in pharmacy-level switching.

	Important for biosimilar makers, the new guidance supports the use of non-US-licensed comparator products to conduct tests and to produce the data needed to demonstrate interchangeability. Even though FDA wants data from bridging studies to foreign-made reference products, manufacturers still may benefit from leeway to obtain samples of biologics that often are less costly outside the United States and can help reduce the cost and time for developing interchangeable therapies. Sponsors developing interchangeable products may be eligible to gain a year of market exclusivity for being the first to develop such a copycat therapy.

	The new guidance also appears less didactic by dropping the frequent use of terms such as “residual uncertainty” and “fingerprint-like” similarity between reference and interchangeable products, which were common in the earlier advisories. FDA here aims to set general standards and requirements for these therapies but notes, however, that the specific data and testing needed to document interchangeability may vary with the structural and functional complexity of the product and with clinical experience with the reference product. Sponsors may seek to justify an exemption from switching studies, and FDA says it will take a flexible approach. 

	In moving forward on standards for interchangeable products, FDA sets the stage for the development and approval of competitive insulin products, which are scheduled to transition to biologic status in March 2020. There is great anticipation that interchangeable insulin therapies will provide important alternatives to current costly diabetes treatments as multiple sponsors move into this field. These issues were discussed at an FDA public meeting in May on the future of biosimilar insulins, just days after the appearance of the interchangeable biologics guidance. As a relatively simple biotech product that has been available as a drug for 100 years (but ineligible for generic competition), manufacturers expect to be able to utilize a rather streamlined and straight-forward process for documenting similarity and interchangeability for these widely used therapies. Firms planning to produce competitive insulin therapies propose that FDA require data from only one, small immunogenicity study, as opposed to multiple switching studies, and that analytic characterization, bridging studies, and reliance on pharmacokinetic and pharmacodynamic data should provide ample support for interchangeable insulins.

	FDA says it plans additional guidance on data needed on product container closure systems and delivery device constituent parts to support the presentation of a proposed interchangeable product. Of interest is how a biosimilar or interchangeable determination may be affected by delivery of insulin through a pump or over-the-counter device.

	So far FDA has not approved any biosimilars as interchangeable, but this is expected to change with this added clarification of regulatory process and requirements. The rising price of insulin therapies has become one of the most contentious issues in the escalating drug pricing debate, with Congressional hearings generating multiple legislative proposals on this issue, many supporting the development of biosimilar and interchangeable products. 

Development of Therapeutic Protein Biosimilars: Comparative Analytical Assessment and Other Quality-Related Considerations, Guidance for Industry

Considerations in Demonstrating Interchangeability With a Reference Product, Guidance for Industry 


	Vol. 43, No. 7
	July 2019
	Pages: 14-15

	When referring to this article, please cite it as J. Wechsler, "FDA Revamps Biosimilar Quality Requirements," 

New guidance documents clarify production standards and processes for developing interchangeable biologic drugs. 

FDA Revamps Biosimilar Quality Requirements

	A provision in a Senate health reform bill has reignited debate over the whether biological products should have to meet product quality standards established by the US Pharmacopeial Convention (USP). FDA officials contend that efforts by the USP to publish product-specific monographs for biological products could hinder the development of innovative products, including competitive biosimilars. USP officials, with support from pharmacists and some patient and healthcare groups, maintain that monograph standards are important for ensuring the safety and quality of all drugs and biotech therapies.

	The debate has intensified as the March 2020 date nears for a cadre of therapies, including insulin, to shift to falling under the rules applying to drugs to those governing biologics. This change is expected to facilitate the development of biosimilar versions of insulin products and other therapies in this group that have complied with USP monographs for years.

	The new policy sought by FDA is contained in 

 recently issued by the Senate Health, Education, Labor and Pensions (HELP) committee, which presents multiple provisions designed to improve national health care programs and access to medicines. These include items to revise patent policy, generic drug testing, and biosimilar oversight as part of efforts to reduce the cost of drugs and biologics.

	The disputed language (section 207 of S. 1895) excludes all biological products regulated by the Public Health Service Act from meeting USP compendial standards, as is the case for conventional drugs. In a recent posting on the FDA website, Janet Woodcock, director of the Center for Drug Evaluation and Research (CDER), and Peter Marks, director of the Center for Biologics Evaluation and Research (CBER), note the 

 biosimilar as a sign of FDA’s success in smoothing the pathway for bringing competitive biotech therapies to US patients. But they also warn that continued innovation in this area could be blocked by “inflexible standards that can’t evolve quickly enough to keep up with technological development,” as might occur if product-specific USP standards are applied to biologics. FDA already has standards in place to ensure the safety, purity, and potency of biological products, Woodcock and Marks observe, and the need to comply with additional standards could extend reviews and delay approvals.

	Similarly, Steven Kozlowski, director of CDER’s Office of Biotechnology Products, explains in another commentary that most widely used biological products do not have USP monographs, and that efforts to 

 for these inherently complex and variable products could “impede technological progress or innovation”. Kozlowski raises the possibility that the manufacturer of an older innovator therapy could ask USP to write a monograph for its product citing patented characteristics that would produce “unnecessary barriers to innovation and progress.”  Unlike small-molecule drugs, which are chemically synthesized to achieve “sameness” with the innovator drug, biological products are highly complex proteins produced from living cells and aim to be “highly similar,” but not the same, as the reference product. 

	Kozlowski maintains that adhering to USP standards would not necessarily prevent products from experiencing quality or safety problems and could make it difficult for a subsequent manufacturer to implement changes, such as a more efficient manufacturing process. While FDA supports USP monograph standards for conventional drugs, it prefers optional standards for biological products that align with the agency’s flexible approach for inherently complex biological products.

	A coalition of pharmacists, public health, and patient organizations supports 

 the authors of the Senate HELP bill to drop the curb on compendial standards for biologics. The group maintains that the proposed policy change would weaken assurances that medicines are safe and of high quality, without doing anything to lower drug costs. USP officials note that mandatory drug quality standards developed by the 

 and the World Health Organization have supported drug development and approval, including biosimilars, in Europe and other regions.  

 Century Cures legislation of 2016 initially included a similar exemption for biologics from USP standards, but the final legislation dropped that provision. More recently, the administration’s budget proposal for 2020 includes a proposal to end the requirement that biologic products comply with USP quality standards. USP and its supporters maintain that public specifications for product purity and potency provide assurances for patient safety and foster competition in the market for biologics, particularly for insulin. FDA’s high-profile response reflects an escalation in the debate over whether the regulatory agency has to accept USP quality standards for all drugs and biologics, or if more flexibility would provide important benefits for the development of new therapies.

The US Senate and the US Pharmacopeial Convention debate the necessity of monographs for biologics. 

FDA Challenges USP Standards for Biologics

	There is great enthusiasm on Capitol Hill and in the Trump Administration for taking action to reduce outlays for prescription drugs, but the path forward is not clear. Multiple House and Senate Committees are weighing in on the issue with a range of measures that differ in style and substance.  In the Senate, the Finance Committee and the Health, Education, Labor and Pensions (HELP) Committee look to build bipartisan support for broad legislative packages, while the House Ways & Means Committee and the Energy & Commerce panel are crafting reform measures with multiple provisions-some conflicting and overlapping.

	Amidst all the proposals to expand patient access to affordable treatments are initiatives to maintain rewards for innovation, such as patent exclusivities and market-based pricing. A prominent administration proposal for bringing down outlays is to peg US prices to those of other industrial nations, such as the United Kingdom, Canada, and Japan. However, the White House has pulled back from that approach, which is strongly opposed by the pharmaceutical industry, and has run into difficulties in looking to limit or alter rebates paid by manufacturers to pharmacy benefit managers.

	A main Democratic proposal aims to authorize the government to negotiate prices on drugs covered by Medicare drug plans, and in some cases by private insurance. While Democratic leaders initially sought to limit negotiations to a short list of high-priced drugs, pressure from progressive party members to expand the scope of such negotiations prompted House speaker Nancy Pelosi to agree to broader price negotiating authority. Some Senate Democrats also back government price negotiations, but diminishing support from the Trump Administration has tamped down Republican interest.

	Moves to permit drug importing have moved forward at the state level, while also gaining broad support in Washington. Florida recently approved a program to bring in drugs from Canada for Medicaid and other state agencies and to authorize more general importing of drugs from outside the United States. But, as with a similar law in Vermont, the Department of Health and Human Services (HHS) has to approve these programs, which has not occurred in the past with similar plans. This time, though, HHS Secretary Alex Azar has backed import flexibility, and some expansion in drug importing is likely to be included in a drug pricing package.

	Patent policy reform also may play a role in the drug pricing debate, as House and Senate Judiciary Committees look to devise patent reform measures likely to spur competition in the prescription drug market. Proposals call for curbs on “gaming” the patent system by drug companies looking to extend monopolies, and for the Federal Trade Commission to crack down on manufacturers that file multiple patents on a drug to delay competition.

	Then there are numerous proposals to reduce drug outlays by Medicare and Medicaid. Pharma companies and patient groups look to cap or limit out-of-pocket (OOP) spending by Medicare Part D beneficiaries and to spread OOP costs over the entire year. Industry also wants to provide co-pay assistance to Medicare beneficiaries, as occurs in the commercial market, and there’s interest in eliminating the current catastrophic phase of the Medicare drug benefit, retaining initial coverage, and a catastrophic phase. Such approaches soften the impact of high drug prices on individuals, but without greatly undermining pharma pricing practices.  

	Industry also supports revisions in current laws that limit drug price flexibility. There is interest in revising the anti-kickback statute to permit government and commercial health plans to devise new payment models for high-priced therapies based on outcomes or long-term effects. Similar policy changes would permit Medicaid to pay for certain medicines over time. Such measures may be linked to policies to prevent brands from “gaming” the system by blocking generic-drug makers from ready access to brand supplies for testing and by discouraging biosimilar prescribing. Biopharma companies continue to fend off such measures and to add in changes opposed by generic-drug makers, such as a limit on the 180-day exclusivity awarded for the first generic to market.

	Meanwhile, industry has mounted an attack on the Trump administration’s requirement that pharma marketers post drug list prices in DTC ads, a high-profile strategy designed to utilize price transparency to limit increases. Leading biopharma companies Merck, Eli Lilly, and Amgen recently went to court to cancel the rule just before its July implementation date, claiming that required disclosure of a drug’s wholesale acquisition cost (WAC) would be misleading because consumers seldom pay that price. The lawsuit also maintains that HHS lacks authority to impose such a rule and that it violates First Amendment protections for advertisers. Pharma companies, instead, propose voluntary posting of more relevant consumer price information, with references to company web sites.  

	Despite all these differences and difficulties, a deal on legislation appears more likely this year than in the past, as consumers, states, payers, and lawmakers look to rein in healthcare and drug spending. Congressional leaders hope to enact initial proposals this summer to have time to negotiate a final package in the fall. Drug pricing legislation will be part of a broader health bill that addresses issues, such as “surprise” medical bills from hospitals, combating the opioid crisis, access to contraceptives, and the administration’s controversial ban on funding research involving human embryos. Progressive Democrats continue to campaign for Medicare-for-all, while Trump still promises a major plan to replace the Affordable Care Act. To move forward, House Democrats and the White House will need to reach some kind of agreement on what is possible this year, and that prospect seems to shift every day.

Congress is weighing in on drug pricing with a range of measures that differ in style and substance. 

Will Congress Enact Curbs on Drug Pricing?

	As part of its ongoing efforts to ensure the availability of high-quality medicines, FDA’s Center for Drug Evaluation and Research (CDER) is rolling out a new system to enhance the evaluation of prescription drug attributes, risks, and control strategies. The Knowledge-aided Assessment and Structured Application (KASA) initiative aims to improve the efficiency, consistency, and objectivity of regulatory quality assessment by collecting structured data on drug substance, product design, and manufacturing process to better assess inherent risks and how they are controlled. CDER’s Office of Pharmaceutical Quality (OPQ) is piloting the program first for abbreviated new drug applications (ANDAs) for generics, with the aim of rolling out the system to generic solid oral dosage forms by year-end. Next will come generic liquids and injectables, followed by new drugs and biologics.

	With more ANDAs and new drug applications (NDAs) filed each year, many involving complex therapies, and increasingly tight assessment time frames for approval set by user fee programs, CDER officials are looking for ways to evaluate submissions more expeditiously and effectively. This new approach asks manufacturers to file structured applications that present key data on product attributes, as opposed to lengthy, text-based narratives. The aim is for OPQ staffers to perform computer-aided analyses that support benefit/risk assessments for comparison across products and facilities. Under development for almost two years, the KASA initiative became more visible when it was discussed publicly and gained unanimous support at the September 2018 meeting of FDA’s Pharmaceutical Science & Clinical Pharmacology Advisory Committee.

	CDER and OPQ leaders presented more detailed information on KASA at the April 2019 PQRI/FDA conference on Advancing Product Quality in Rockville, MD (1). KASA aims to provide a structured assessment of an application that summarizes key information and “minimizes text-based narratives,” explained OPQ Deputy Director Lawrence Yu. Advances in information technology not only generate more information on key quality attributes, Yu pointed out, but also allow for a faster, more complete assessment. He directed manufacturers to an article outlining the KASA program in the 

International Journal of Pharmaceutics: X

 for further information on the program and its approach (2).

	Similarly, at the April 2019 CMC Workshop sponsored by the Drug Information Association (DIA), Geoffrey Wu, associate director of OPQ’s Office of Lifecycle Drug Products (OLDP), described how the KASA initiative will capture and manage knowledge of drug product quality to establish a product risk control strategy for lifecycle management. This approach will avoid inconsistent application of quality standards and help prevent shortages and quality failures of marketed drugs. KASA also will assess manufacturing risks and controls in order to “flag the potential need for a pre-approval inspection based on multiple factors and complexities using standardized risk thresholds,” Wu noted. This will involve examining the control strategy for the manufacturing facility, including site inspection history, based on a standardized assessment of risks compared across products and facilities.

	The modern drug assessment system under KASA will build on algorithms of risk and support computer-aided analysis for a structured assessment of an application. The process begins with an objective evaluation of risk that considers key critical quality attributes, enabling OPQ staff to then focus on more risky products. The analysis considers the severity of possible harms and the detectability of future failures to be able to compare risks across products and determine if attributes are within or outside acceptable ranges. With such information, CDER still may approve a risky product, but with a recognition of the need for greater oversight to control for possible future problems.

	In making the case for KASA at the PQRI meeting, OLDP Director Susan Rosencrance observed that applications for new drugs and generics composed of unstructured text can be a hindrance to an efficient agency assessment of product quality. Too often, she said, the important information on how an applicant controls risk “is lost in hundreds of pages of text.” This may encourage a reviewer’s quality assessment to be more subjective, leading to inconsistent decisions by the agency.

	Drug applications that present information in prose require reviewers to do “a lot of hunting and pecking” to pull out key data, added Mary Ann Slack, director of CDER’s Office of Strategic Programs. To move forward, FDA plans to develop and test electronic data standards for submitting product quality and chemistry, manufacturing, and controls (CMC) data to the agency, Slack explained. This will be described in draft guidance slated for publication by March 2020 to further explain how future applications should present data files that can be entered into FDA’s drug data system to check ranges and areas to review more closely.

	KASA is part of broader CDER efforts to modernize its drug regulatory program. This includes reorganizing the Office of New Drugs, developing new IT platforms and applications, establishing quality metrics, and building the emerging technology program to promote new drug design and manufacturing strategies. More consistent and objective regulatory assessments under KASA fits these broader goals by helping FDA achieve more first-cycle approvals for manufacturers and more affordable and accessible medicines for patients.

4th FDA/PQRI Conference on Advancing Product Quality


	Vol. 43, No 6
	June 2019
	Pages: 14, 38

	When referring to this article, please cite it as J. Wechsler, "FDA Advances New Approach to Drug Quality Assessment," 

CDER’s KASA program seeks manufacturer data on drug attributes and risks to inform oversight.