Utilizing Generic Drug Awareness to Improve Patient Outcomes with Dr. Sarah Ibrahim

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Dr. Roach: Welcome to “Q&A with FDA.” In this podcast series, we aim to answer some of the most frequently asked questions that we’ve received from the public. My name is Dr. Sara Roach, and today’s topic is improving patient outcomes with generic drug awareness.

Lack of awareness of the rigorous FDA application process that ensures generic drugs meet high standards may lead some patients who are switched to a generic medication to hesitate in taking it. Discontinuing treatment can lead to decreased medication adherence and, ultimately, worse health outcomes.

Today we are once again joined by Dr. Sarah Ibrahim, Associate Director for Stakeholder and Global Engagement in the Office of Generic Drugs, OGD, in FDA’s Center for Drug Evaluation and Research, or CDER.

Dr. Ibrahim, thank you for joining us today. The last time you were on our podcast was in May 2023, speaking with our audience about the importance of generic drugs and FDA’s standards for their approval. We appreciate your passion for improving generic drug literacy.

Dr. Ibrahim: It’s great to be back, and yes, I am passionate about enabling patient access to generic drugs and committed to informing healthcare professionals about their benefits. Enhancing public literacy about generic medications is crucial to improving patient outcomes. Pharmacists – and all health care professionals - have such a large impact on patients when it comes to generic drug literacy, and this translates directly into drug usability.

As a pharmacist myself, I know how busy it gets in high volume pharmacies and clinics, but I cannot stress how important it is for pharmacists to talk with patients about their generic medications BEFORE switching from a brand name drug to a generic drug to address any negative perceptions that may exist.

Dr. Roach: Can you tell us about the research FDA’s Office of Generic Drugs is conducting and funding to better understand how we can best educate and engage health care providers and patients about generic drugs?

Dr. Ibrahim: We conduct internal and external research to enhance public understanding of generic drugs, guiding our educational efforts. This research, strengthened by the Science and Research program under the Generic Drug User Fee Amendments, supports OGD's scientifically rigorous assessment of generic applications.

One example is that we recently published a qualitative study conducted among focus group participants with chronic obstructive pulmonary disease or asthma who were actively using a brand-name drug that was a dry powder inhaler - to explore patients’ attitudes and perceptions related to generic dry powder inhaler substitution, along with patients’ views of generic drug quality, efficacy, design, and usability.

Dr. Roach: What were the results?

Dr. Ibrahim: Overall, we found that patients viewed generic drugs as more accessible than brand–name drugs, in part, because participants thought generic drugs were more likely to be covered by insurance. Participants generally suggested that generic medications were similar to their brand-name counterparts, with the same active ingredients, although perceptions of efficacy, safety, and quality were mixed. Many of these perceptions were caused by uncertainties about how the generic differs from the brand-name drug.

Most participants in the study also commented on the look or feel of the generic dry powder inhaler device, which was slightly different than the brand-name product, and considered how this difference may affect their use of the device. Now these aspects tend to relate to convenience (such as fitting the device in a purse) and ease of use (such as fewer steps to perform) more so than proper use. This highlights the critical role of patient counseling by healthcare professionals during the transition from brand-name to generic medications.

Alternatively, participants did show some hesitation in their ability to properly use the generic device, particularly for the first time. In many cases, participants seemed willing to change to the generic version, especially if they thought there would be a financial benefit.

And in line with prior studies, participants expressed some negative perceptions of switching from brand-name to generic, much of which seemed to stem from the fact that they were not first asked or informed about the switch. Patients want to be actively involved in decisions regarding their medication and have control over their health conditions.

Dr. Roach: This research supports the need for more effective outreach.

Dr. Ibrahim: Exactly right. We think there are opportunities for FDA, our partners in health care professional organizations, and patient advocacy organizations to improve generic drug literacy among adults, adolescents, and health care providers.

This type of research helps support FDA's ability to approve generic drugs that have demonstrated sameness to the brand-name product, but they may have minor differences in design and usability, which do not affect outcomes for patients. This is especially important for complex generic products that are more challenging to develop, such as inhalers or autoinjectors.

Dr. Roach: It’s been my experience that taking the time to talk with patients about switching from brand-name to generic drugs can increase their confidence in taking generic medication, beginning with conveying FDA’s commitment to protecting the health of the American public by holding ALL approved products to high standards of quality, safety and efficacy.

Dr. Ibrahim: We already know it, but it’s important for health care providers and pharmacists to share their knowledge with patients that a generic drug must show bioequivalence to the brand-name, or reference listed drug.

Now while generic drugs might differ in some ways from the brand drug, such as using different inactive ingredients, the generic firm must provide evidence to support that these differences do not make the generic drug less safe or effective than the brand drug to be approved. Sometimes this concept is not clear to patients.

Dr. Roach: With all the awareness about food allergies, food intolerances and food preferences, there are many patients concerned about inactive ingredients.

Dr. Ibrahim: Very true. Some generics can contain different inactive ingredients than their brand name counterparts. For example, colors and flavorings may be different in some products, but FDA will not approve a generic drug if these differences affect the safety or effectiveness of the generic drug. This may not concern most people, but for others this could be a source of confusion or negative perception.

So, it is helpful for patients to be aware that although the inactive ingredients may differ between some generic and brand drugs, the generic must be shown to be no less safe or effective than the brand drug despite such differences.

Dr. Roach: Finding out if an inactive ingredient is included in a particular brand or generic drug isn’t always the easiest information to find if you don’t know where to look.

Dr. Ibrahim: No, it isn’t, which is one of the reasons it’s so important to educate patients. If you know that a patient has a certain allergy or intolerance with a prescription drug, check the “Description” section of the labeling or package insert. In nonprescription or over-the-counter drug products, inactive ingredients are identified on the “Drug Facts” label in the “Inactive Ingredients” section.

Let’s take gluten as an example. We would expect any oral drug product containing wheat gluten as an added ingredient to be labeled as containing wheat gluten.

The possible addition of wheat gluten to oral drug products as an inactive ingredient rarely, if ever, occurs, and the FDA is not aware of the intentional and purposeful addition of wheat gluten as an inactive ingredient to any oral drug product currently marketed in the U.S. If the list of ingredients does not mention wheat gluten or wheat flour, then the product should not contain gluten in an amount that would harm a typical, non-refractory individual with celiac disease.

Dr. Roach: But wheat gluten may be present at low levels as an impurity in ingredients that are derived from wheat, such as wheat starch.

Dr. Ibrahim: There are drug ingredients and categories of ingredients derived or potentially derived from wheat, that may contribute gluten to a unit dose of an oral drug product. For example, we estimate based on drug formulation information that wheat, starch, and other ingredients derived from wheat would contribute no more than 0.5 mg of gluten to a unit dose of an oral drug product. This amount is less than may be found in a single, 30-gram serving of food labeled gluten-free according to FDA’s regulations. But for those that cannot tolerate any amount of gluten, or when in doubt about the source of an ingredient, its best to contact the manufacturer. Though the pharmacist or technician may not have time to do this, they can educate patients to do so.

Dr. Roach: Other factors that may differ and affect patient perceptions of generic drugs involve the physical characteristics of the generic product, such as the shape, color or size of a tablet or capsule. If patients aren’t expecting a change in the physical characteristics of their medicine, they may not take it, and this could affect patient compliance or could lead to medication errors.

Dr. Ibrahim: You are right, studies indicate that patients are more likely to stop taking their generic medications when they experience a change in their drugs' physical appearance, and FDA has recommended that generic drug manufacturers consider physical attributes when they develop generic products. FDA considers such differences before approving generic drugs and will ask for modification if there are concerns because of the differences in physical characteristics.

I would also like to note that a difference in drug delivery system may be allowable for complex generic drugs, such as certain inhalers, which may lead to patient concerns if the patients are not aware of the fact that FDA has carefully evaluated any differences as part of the generic drug approval process.

Because patients may automatically be switched to a generic when they are expecting to receive a brand name drug, it is SO important for pharmacists to make the patient aware of the change, and to reassure them that they are receiving the correct drug.

Dr. Roach: We receive questions about the amount of variability permitted by FDA in generic drugs. Can you speak more about this?

Dr. Ibrahim: There may be a slight, but not medically significant, level of expected variability between a brand-name medication when compared to a generic version. The important thing to note is that this is just as true when comparing one batch of brand-name product compared with the next batch of the same brand-name product. This variability can and does occur during manufacturing, for both brand-name and generic medicines. From a quality perspective, there is an acceptable range into which all products, brand or generic, must fit.

Dr. Roach: Another topic that frequently comes up in the inquiries that FDA receives from the public, is the issue of authorized generics. For example, a seemingly generic version of a brand name drug may be dispensed, but the insurance company claims that it is not truly a generic and thus may cost more.

Dr. Ibrahim: I’m glad you brought this up because it often leads to confusion, especially when insurance will not cover the authorized generic. The term “authorized generic” drug is commonly used to describe an approved brand name drug that is marketed under the brand company’s new drug application but without the brand name on its label – this can be thought of as the brand-name company’s own generic product. 

An authorized generic version of a tablet or capsule may have a different color or marking, but other than the fact that it does not have the brand name on its label, it is the same drug product as the branded product and may be marketed by the brand name drug company, or by another company with the brand name company’s permission.

FDA requires that the company notify the FDA if it markets an authorized generic, and we publish a list of all reported authorized generics on our website, which is updated quarterly.

And even though the authorized generic is the same as the brand name product, in some cases a company may choose to sell the authorized generic at a lower cost than the brand name drug – so it may appear in that way, even more like a generic.

In terms of questions about insurance, it’s important to know that FDA’s authority does not extend to drug pricing, or to the policies of insurance companies.

Dr. Roach: There have been cases where FDA has approved a generic but later found that the product was not in fact bioequivalent. Would you expand upon situations like this?

Dr. Ibrahim: Despite FDA’s post-market surveillance and risk assessment programs, on rare occasions that does happen. When CDER staff identify new information about the safety of a drug, we investigate the issue and consider appropriate action, and this is also applicable when a generic drug product no longer demonstrates bioequivalence.

The agency receives and analyzes reports of adverse events – and product problems – to determine if these adverse events were caused by a drug. CDER uses these reports, along with other sources of drug safety data, to monitor the safety of approved drugs and therapeutic biologic products. When new potential safety issues are identified, FDA conducts a thorough and rigorous review of the available data before determining what, if any, actions are appropriate.

For example, in 2016 there was a situation where FDA began to receive reports of lack of effect associated with two specific generics for Concerta, which is used for the treatment of ADHD, shortly after the initial approval of each product. There was also an authorized generic available on the market under a licensing agreement, which was identical to Concerta, though not marketed under the brand name.

FDA evaluated the overall number of complaints for these two generic products relative to the brand-name and authorized generic products and found substantially more complaints for the two generic products – which prompted a further investigation.

The agency then conducted a multi-disciplinary review of the products, including an evaluation of adverse event reports, a review of the data that were submitted with the generic applications, testing of the drug products in FDA labs, and broad interdisciplinary consultation with FDA physicians, pharmacists, chemists, and other agency scientists and experts to discuss the new information.

Ultimately, FDA asked that within six months, the companies of the two generic products confirm the bioequivalence of their products using revised bioequivalence standards, or to voluntarily withdraw their products from the market.

In the end, FDA changed the therapeutic equivalence rating for both companies’ products in the Orange Book from AB to BX, to convey that the data were insufficient to show that the products provide the same therapeutic effect as Concerta or the authorized generic. The generic products downgraded to BX could still be prescribed but they were no longer deemed therapeutically equivalent with the brand product.

Dr. Roach: That is an excellent example of how parents and caregivers through MedWatch reporting helped FDA identify and course correct. Switching gears a bit, what should pharmacists and other health care professionals tell patients who are concerned with generic drug products manufactured overseas?

Dr. Ibrahim: No matter where any FDA approved drug is made, it is required to be manufactured under the same strict standards as the brand-name medicine. This means that it must meet the same batch requirements for identity, strength, purity, and quality. The same standards apply to FDA-approved drugs (brand or generic) regardless of whether they are manufactured within or outside the US.

Dr. Roach: And FDA inspections are an important tool to help ensure facility and process quality.

Dr. Ibrahim: I couldn’t agree more. FDA performs a risk-based assessment of facilities listed in a drug application, which includes the facilities used to manufacture a drug, laboratories, and packaging facilities. FDA inspectors may go to the generic drug manufacturer's facility to verify that the manufacturer is capable of making the medicine consistently and to check that the information the manufacturer has submitted to FDA is accurate. Or FDA may request to remotely interact with a facility to evaluate compliance with required manufacturing practices. CDER also uses inspection information from regulatory partners in other countries. These alternative tools to inspection allow CDER to obtain information about manufacturing facilities without physically visiting the facility.

Dr. Roach: Recently, FDA identified significant unexplained anomalies in data from a clinical research organization, or CRO, based in India that indicated falsified data submitted in support of a number of generic drug and brand drug applications, and outlined significant data integrity concerns for bioequivalence studies.

Dr. Ibrahim: We take data integrity issues very seriously. In this case, FDA issued an initial general correspondence letter to the CRO outlining significant data integrity concerns for bioequivalence studies conducted by the CRO and submitted in support of abbreviated new drug applications for generic drugs, or ANDAs.

FDA then issued a second general correspondence letter to the CRO describing the agency’s determination that their study data must be rejected, and required that sponsors of approved, tentatively approved or pending abbreviated and new drug applications repeat the bioavailability/bioequivalence studies, when those studies are essential to approval, using an entity other than this particular CRO or any other organization with known unresolved data integrity concerns.

FDA also determined that data from the CRO were not acceptable to support a determination of safety or effectiveness for brand-name drugs, or to show affected generic products are bioequivalent to brand-name products.

Product safety, efficacy, and quality information is only valuable to consumers and the agency when it is reliable, truthful, and accurate. When the FDA finds that manufacturers lack sufficient controls over the integrity of their data, or worse, in extremely rare cases when firms intentionally violate such controls, those manufacturers’ practices raise questions about the accuracy, reliability, and truthfulness of all the data and information they collect and report to the FDA about safety, efficacy, and quality of their drug products.

Dr. Roach: How do you convince busy health care professionals of the importance of taking the time to have these conversations about generic drugs with their patients?

Dr. Ibrahim: Patient counseling is incredibly important in practice. Talking to patients about their generic drugs improves usability, compliance, and outcomes, and can save the healthcare professional time in the future - addressing questions about why a medication looks different - or worse, time necessary to get back on track with a patient who discontinues therapy because of uncertainty around the drug they received. And keep in mind that patients may be switched to multiple generics of the same brand name product over the course of a year, which can add to the confusion.

Simple things that don’t take much time, like providing patient education materials about generic drugs, or including a sticker on the bag or prescription bottle, can make a big difference. We offer a lot of patient education materials on our webpage, including handouts, flyers, and infographics, that we hope are helpful for healthcare professionals.

Dr. Roach: Those patient education materials are linked in the resources section of our podcast webpage.

Thank you again Dr. Ibrahim for talking to us about the importance of generic drug literacy. And thanks to our audience for listening to “Q&A with FDA”. The full podcast and transcript of this recording is available at fda.gov/qawithfda. Many of our episodes offer continuing education credits for health care professionals, so be sure to visit fda.gov/qawithfda for more details. If you are looking for additional learning or continuing education credit opportunities, including live and home study webinars, you’ll also want to check out fda.gov/CDERLearn and fda.gov/DDIWebinars. And if you have questions about this episode, or anything drug-related, email us at druginfo@fda.hhs.gov.

Resources:

• Generic Drugs: Questions & Answers
• Questions and Answers Regarding Methylphenidate Hydrochloride Extended Release Tablets (generic Concerta) made by Mallinckrodt and UCB/Kremers Urban (formerly Kudco)
• Size, Shape, and Other Physical Attributes of Generic Tablets and Capsules - Guidance for Industry
• FDA’s List of Authorized Generics
• Improving Medication Adherence and Patient Experience by Researching Patient Perceptions of Generic Drugs
• Patient Education | FDA