BIO Principles on Patient Safety in the Substitution of Biologic Products
October 29, 2012
In August, BIO released Principles on Substitution for Biologic Products. Read the Principles here.
ASBM Statement on Automatic Substitution
October 26, 2012
The Patient Protection and Affordable Care Act passed by Congress and signed into law by President Obama in March 2010, contained a provision establishing an abbreviated pathway for the approval of biosimilars (also referred to as followon biologics, or subsequent entry biologics) in the U.S.
In February 2012, the U.S. Food and Drug Administration (FDA) released a set of three draft guidance documents on biosimilar product development to assist industry in developing such products in the U.S. The guidance documents outlined the FDA’s current thinking on key scientific and regulatory factors involved in submitting applications for biosimilar products to the agency but did not provide any insight on how the agency would handle, “interchangeable biosimilars.” In fact, the regulatory agency sent an unambiguous signal on this topic when it stated in the draft guidance “[t]his document is not intended to provide an overview of FDA’s approach to determining interchangeability because FDA is continuing to consider the type of information sufficient to enable FDA to determine that a biological product is interchangeable.”
On May 24, 2012 ASBM Chairman Richard Dolinar, M.D., convened a working group of Advisory Board members to discuss the elements of a physician notification policy for interchangeable biosimilars that prioritizes patient safety and protects the relationship between physicians and their patients but also respects the sovereignty of pharmacists as healthcare providers. As ASBM continues to work with stakeholders to develop an official position statement on this very important topic there are a few key principles that ASBM believes must be reflected in any policy recommendation:
(1) Physicians have the authority to specify “do not substitute” for biological products and that specification overrides any policy – e.g. by payers or state law – that would have substitution be the standard or default practice;
(2) Physicians and pharmacists should work collaboratively to ensure that the treating physician is aware of the exact biologic – by manufacturer – given to a patient in order to facilitate patient care and accurate attribution of any adverse events that may occurs; and
(3) The timing of the notification process must not impose an undue burden on the pharmacist and need not be in advance of a substitution being made but must be timely enough to facilitate accurate record keeping and attribution of adverse events by the physician.
BIO Principles
October 25, 2012
BIO developed the bellow set of Biosimilar Principles to serve as recommendations for Congress for creating a biosimilar pathway:
As Congress explores the creation of any regulatory pathway for follow-on biologics, it is essential that Congress recognize and adopt the following key principles:
Ensure Patient Safety. Patients should not have to accept greater risks or uncertainties in using a follow-on product than an innovator’s product. Thus, Congress should:
- Ensure that approval of follow-on biologics is based on the same rigorous standards of safety, purity, and potency applied by FDA for the approval of pioneer biotechnology products.
- Recognize that clinical trial evidence and data are fundamental for evaluating and demonstrating the safety and effectiveness of a follow-on biologic, and must be conducted on a product-by-product basis. In particular, immunogenicity testing is necessary to avoid putting patients at risk of adverse effects from immune reactions.
- Not preclude adequate post-market evaluation of follow-on biologics products. It is critical that follow-on biologics are properly evaluated through post-marketing surveillance and post-marketing clinical studies as needed.
- Avoid specific constraints on the scientific conclusions FDA can reach in evaluating the similarity or comparability of follow-on biologics.
- Ensure that follow-on biologics will be assigned a non-proprietary name readily distinguishable from that of the innovator’s version of the product. Assigning the same name to a product that is not the same would be confusing and misleading to patients, physicians, and pharmacists, could result in inadvertent substitution of the products, and would make it difficult to quickly trace and address adverse events that may be attributable to either the innovator or follow-on product.
Recognize Scientific Differences Between Drugs and Biologics. Biologics are much more complex than small molecule chemical drugs. Thus, Congress should:
- Recognize that the methods used to show that one chemical drug is the same as another are different from and insufficient for biologics. Thus, versions of a biological product made by different manufacturers must be evaluated on a case-by-case basis, because they will differ from each other in certain respects. The methods used by innovators to demonstrate continued safety and effectiveness after a manufacturing process change are insufficient to demonstrate safety and effectiveness of a follow-on biologic made by a different manufacturer using a different process.
- Recognize that, as innovator companies’ experiences with respect to pioneer biotechnology products have shown, and as FDA has long emphasized through its regulation and guidance, small product or manufacturing differences in biologics can result in significant safety and/or effectiveness differences.
Maintain the Physician-Patient Relationship. Small molecule generic drugs can be designated as therapeutically equivalent and may be dispensed interchangeably with innovator products without physician knowledge. In contrast, the current state of science is not sufficient to establish interchangeability for complex follow-on biologics. Indeed, FDA recently stated that it “has not determined how interchangeability can be established for complex proteins.” Accordingly, Congress should ensure that patients are not given follow-on biologics unless expressly prescribed by a physician.
Preserve Incentives for Innovation. In order to preserve incentives to research, develop and manufacture new innovative therapies and cures, as well as new indications for such products, any statutory pathway for follow-on biologics must:
- Include substantial non-patent data exclusivity, during which time follow-on manufacturers could not rely on FDA’s prior approval of pioneer biologics to support approval of their own products. Such data exclusivity is necessary because a follow-on biologic may be similar enough to a pioneer biologic for regulatory approval purposes, but different enough to avoid the innovator’s patents. Thus, non-patent exclusivity is necessary to maintain effective market protection. Further, the fledgling nature of the biologics industry, its heavy dependence on access to significant amounts of high-cost public and private investment capital, and the high risks and costs involved in the development of new biologic medicines all warrant a substantial period of exclusivity.
- Respect intellectual property and other legal rights. Follow-on biologic products should not be approved until after all statutory protections, including data exclusivity and patent protections, are no longer available for the approved pioneer product. Any follow-on biologics pathway should fully respect existing trade secret protections for innovators’ data and not permit the use of protected data for the purpose of approving follow on products. It also must not abrogate or limit constitutional or statutory rights of patent holders to protect against infringement.
- Provide adequate notice and process rights. Any follow-on biologics regulatory pathway should ensure that any patent challenge involving the follow-on biologic product will be litigated prior to marketing approval of the follow-on product, in order to protect the innovator’s intellectual property rights and avoid confusion in the medical, patient, and payer communities. Further, any follow-on biologics regulatory pathway should not create special patent litigation rules that favor follow-on biologics manufacturers.
- Ensure Transparent Statutory and Regulatory Processes. Manufacturers of innovator products should be provided full and fair opportunities to engage Congress and other stakeholders in a meaningful public process. Establishing a balanced and rigorous statutory pathway for follow-on biologics requires deliberative evaluation of numerous complex scientific, legal, intellectual property and economic issues.
Further, any such pathway must require that FDA follow a transparent and public process in determining data requirements for the approval of specific follow-on biologics.
Continue to Prioritize FDA Review and Approval of New Therapies and Cures. Any applications for approval of follow-on biologics will raise novel and complex questions of science and law, requiring substantial time and additional resources to ensure a thorough regulatory review for safety, purity, and potency. In order to avoid slowing down FDA’s review and approval of new therapies and cures, many for currently untreatable and serious diseases, Congress must ensure that workload associated with these new applications does not harm FDA’s ability to efficiently review new drugs and biologics, and that new treatments continue to have the highest review priority.
More information on the Principles can be found on BIO’s website.
Inside Health Policy: Stakeholders Debate Biologic Product Drift’s Impact On Biosimilars
October 25, 2012
One biosimilar developer is pushing FDA to address how changes to innovator biologics over time could affect biosimilar products that reference them, advocating for the agency to use comparability standards as a basis for determining biosimilarity, allow biosimilar determinations based only on one version of an innovator product if drift occurs and investigate ways to slow down innovator activities that create drift. Other sources said, however, that biologic products naturally drift over time and manufacturing improvement changes should not be prevented by FDA.
Concerns over biologic drug product drift — product changes that can occur over time as a result of manufacturing changes — are resurfacing as industry groups continue to push FDA to provide more information on how it will determine biosimilar interchangeability.
Read the article on Inside Health Policy.
Inside Health Policy: Stakeholders Debate Biologic Product Drift’s Impact On Biosimilars
October 25, 2012
One biosimilar developer is pushing FDA to address how changes to innovator biologics over time could affect biosimilar products that reference them, advocating for the agency to use comparability standards as a basis for determining biosimilarity, allow biosimilar determinations based only on one version of an innovator product if drift occurs and investigate ways to slow down innovator activities that create drift. Other sources said, however, that biologic products naturally drift over time and manufacturing improvement changes should not be prevented by FDA.
Concerns over biologic drug product drift — product changes that can occur over time as a result of manufacturing changes — are resurfacing as industry groups continue to push FDA to provide more information on how it will determine biosimilar interchangeability.
Read the article on Inside Health Policy.
Phoenix Forum
October 5, 2012
The Alliance for Safe Biologic Medicines (ASBM), the International Cancer Advocacy Network (ICAN) and AZBio hosted “Biosimilars Policy Forum: Ensuring Patient Safety” on September 27, 2012 in Phoenix, AZ, to discuss the complex challenges the Food and Drug Administration (FDA) faces as it seeks to establish a regulatory pathway that will lead to the approval of biosimilars in the U.S.
Alliance for Safe Biologic Medicines Responds to Updated EMA Q&A on Biosimilars
October 2, 2012
WASHINGTON – On September 27, 2012 the European Medicines Agency (EMA) released a revised version of their 2008 Question and Answer (Q&A) document differentiating the regulatory standards for biosimilar medicines from the standards used to support generic chemical medicines. ASBM Chairman Richard Dolinar, MD, released the following statement in recognition of the importance of that Q & A document:
“We see the changes the EMA made as a clear indication that Europe, and the EMA in particular, continue to distinguish between generics and biosimilars. As a practicing physician, I am pleased that the EMA have taken steps to guide the public to consult with both their physician and their pharmacist before making any changes to their medicines and recognize that biosimilar does not mean identical. We support their efforts to more clearly define the differences between biosimilars and generics.”
About the Alliance for Safe Biologic Medicines
The Alliance for Safe Biologic Medicines (ASBM) is an organization composed of diverse healthcare groups and individuals from patients to physicians, innovative medical biotechnology companies, and others who are working together to ensure patient safety is at the forefront of the biosimilars policy discussion. Visit us at www.SafeBiologics.org.
###
Alliance for Safe Biologic Medicines Responds to Updated EMA Q&A on Biosimilars
October 2, 2012
WASHINGTON – On September 27, 2012 the European Medicines Agency (EMA) released a revised version of their 2008 Question and Answer (Q&A) document differentiating the regulatory standards for biosimilar medicines from the standards used to support generic chemical medicines. ASBM Chairman Richard Dolinar, MD, released the following statement in recognition of the importance of that Q & A document:
“We see the changes the EMA made as a clear indication that Europe, and the EMA in particular, continue to distinguish between generics and biosimilars. As a practicing physician, I am pleased that the EMA have taken steps to guide the public to consult with both their physician and their pharmacist before making any changes to their medicines and recognize that biosimilar does not mean identical. We support their efforts to more clearly define the differences between biosimilars and generics.”
About the Alliance for Safe Biologic Medicines
The Alliance for Safe Biologic Medicines (ASBM) is an organization composed of diverse healthcare groups and individuals from patients to physicians, innovative medical biotechnology companies, and others who are working together to ensure patient safety is at the forefront of the biosimilars policy discussion. Visit us at www.SafeBiologics.org.
###
ASBM, ICAN and AZBio Discuss Patient Safety during Phoenix Forum
October 1, 2012
PHOENIX – The Alliance for Safe Biologic Medicines (ASBM), the International Cancer Advocacy Network (ICAN) and Arizona Bio hosted “Biosimilars Policy Forum: Ensuring Patient Safety” in Phoenix, AZ. The forum provided an opportunity for robust discussion of the complex challenges associated with ensuring the safety of all biologic medicines, as well as the benefits that patients will see from the availability of biosimilars in the U.S.
Members of the patient, physician, pharmacist and research communities provided an educational overview of biologic medicines and the biosimilars that aim to replicate them.
Following a “Biosimilars 101” presentation by ASBM Chairman Dr. Richard Dolinar, Joan Koerber-Walker, president and CEO for AZBio, moderated a panel discussion during which the participants addressed the challenges of ensuring patient-safety as biosimilars are approved in the U.S. Because biosimilars will not be identical to the products they copy, FDA must content with several safety considerations that are generally not an issue for generic drugs. These include what scientific name a biosimilar should be given and how a biosimilar will be deemed “interchangeable” in light of having structural differences from the original product.
Panelists were Philip J. Schneider, Professor and Associate Dean of the University of Arizona College of Pharmacy; Eric Thompson, PhD, Director of Biomarker Research for Paradigm and International Genomics Consortium; Brett Johnson, PhD, International Cancer Advocacy Network and Patricia Lucente, who is a patient advocate with the Colon Cancer Alliance.
“The Alliance for Safe Biologic Medicines has been working to support regulatory efforts to safely bring biosimilars to our country for the past two years by providing the FDA with our recommendations, conducting educational webinars and by recently releasing a survey on physician practices relevant to ensuring safe use of biologics. It is essential that patient-safety is the cornerstone of the biosimilar pathway,” said Dr. Dolinar. “We have held several educational forums to raise awareness on these life-saving, yet extremely complex medicines, and it has been a pleasure to hold such a great event in my hometown with ICAN and AZBio and all of the participants.”
Biologics are used to treat cancer, rheumatoid arthritis and other debilitating diseases. On February 9, 2012, the FDA announced the publication of draft guidance documents relating to the developments of biosimilars, which are similar to, but not exact copies of biologics. The guidance documents were a significant step in establishing a biosimilars pathway and as the FDA moves forward, ASBM will continue to work to ensure patient safety remains the priority.
The U.S. Food and Drug Administration (FDA) is currently developing a regulatory pathway that will ensure biosimilars are safe for patients as they are introduced in the U.S.
About the Alliance for Safe Biologic Medicines
The Alliance for Safe Biologic Medicines (ASBM) is an organization composed of diverse healthcare groups and individuals from patients to physicians, innovative medical biotechnology companies, and others who are working together to ensure patient safety is at the forefront of the biosimilars policy discussion.
###
