Quality standards at the heart of generic development

By Maggie Lynch

- Last updated on GMT

(Image: Getty/Artisteer)
(Image: Getty/Artisteer)

Related tags Usp Fda Generics

Developing generics that receive approval is more efficient when quality and production standards exist, explains USP CEO.

Ron Piervincenzi (RP​), CEO of US Pharmacopeia (USP), spoke with in-PharmaTechnologist (IPT​) on what it is doing to generate greater access to generic medicines, particularly complex medicines​.

USP has collaborated with the US Food and Drug Administration (FDA) since the latter’s beginnings, most recently though, the two regulatory organizations worked together to encourage drug competition and improve access to generics.

The FDA released its Drug Competition Action Plan​, which it has since made additions to in order to improve the availability of complex generics, and USP also released its Generics Access Plan​.

Additionally, USP, a non-profit standard-setting organization, convenes with regulators, industry representatives, payers, and health care practitioners to identify ways to support generic development.

Ron Piervincenzi, CEO of USP

With generic medicine savings the US $1.5tn (€1.3tn) over the past 10 years, which to the USP determines that “generics represent a health care success story.”

According to a report​ released by the Association for Accessible Medicines (AAM), brand name drugs represent 10% of drugs on the market but 77% of drug spending. However, when generics are available these options are chosen 97% of the time.

However, the USP affirms that public quality standards can help facilitate greater generic competition and, in turn, increase generic options available to patients and increase savings.

IPT: What is USP working on, in respect to boosting generic development and access?

RP:​ The work we do, with respect to generics access, is exactly at the heart of what we’ve always done for 200 years. Quite literally it’s a natural extension of the science we began in 1820 – that is setting the quality standards for medication that has a single, common bar for all the medications in the US and 140 other countries.

Setting quality standards plays an important role in generic approvals, quality testing, and market quality check, even in the development of a new generic.

IPT: Would the cost difference between generics and name brand drugs be large enough to be beneficial for patients, especially with complex drugs?

RP:​ I suppose it’s an impossible thing to know. We prioritize what we work on based on what the FDA has published.

In the factory marketplace, one new generic doesn’t reduce price; typically, it starts to make a small difference, but when three or five generics enter in the market that’s when you start to see a bigger impact.

That data was helpful to us at USP – if we know that our standards help generic manufacturers make new drugs and get them approved, and we know from the FDA’s data that if you have three, four, five competitors or more, then it gives us a chance to help prioritize our work.

When the FDA started to announce a list of drugs that had little to no competition, it started as a couple hundred, now there are 523 drugs that do not have enough competition to reach that four or five competitor mark. So, we’ve looked at those 523 drugs as a prioritization tool to make sure we have standards for as many of those drugs as possible [so generics can be developed] – we already have many, and there are others we are working on.

Of those 523, some of those are complex drugs, which may include drug-device combinations, metered dose inhalers, or maybe even, in some cases, the medicines themselves are complex to manufacture. We recognize that, but the role our standards play is really no different – in fact, it may be more helpful to the industry to have the quality bar set.

IPT: Oncology and diabetes are two drug classes with the least amount of generic savings? What can be done to increase generic savings in these drug classes?

RP:​ In that space [oncology and diabetes], the vast majority of medicine are chemical medicine generics or chemical medicines, in general. Of course, that’s where most of our standards are. We also work in other modalities including biologics and other areas.

We are aware in certain areas, including oncology and diabetes, where you have a larger use of biologic products, which are generally more expensive, you’ll see fewer savings. That said, even in those spaces, there are generics in use and they can play a very important role.

IPT: What can be done for those drug classes to increase generic savings?

RP:​ We look at this as a few phases – the places where standards are most useful.

The most obvious, if I work backwards, is when you have a multi-manufacturer marketplace, and our standards are used to make sure they all meet the same quality bar – with approval and quality checks along the way.

Moving upstream, at the introduction of generic. It is essentially easier to create a new drug approval if they have USP standard available then if they don’t. What that tells us is that regardless of the number of drugs, but especially when there are fewer, the existence of standards help companies create them.

IPT: How can the industry and regulatory agencies aid in making complex drugs generic?

RP:​ Our primary tool is our standards. We’ve spent the last two years reaching out to innovators in generics and we’ve had good success all along, but we’ve had increasingly good success with partnerships to help develop the necessary standards for complex generic where it’s harder, it’s more work, and the information is often held in fewer companies’ hands.

We have dozens of staff dedicated, and another hundred or so who participate in education programs, in what we call capability building. These are workshops held in countries – in the US sometimes, but because most of our medicines aren’t from the US, most of the education programs are conducted in the countries you’d expect: India, China, and Brazil. In these workshops, they are sometimes focused on one very high profile standard, sometimes quality overall, but the latest technologies and how to use them – they’re education tools.

In this context, when we’re talking about the more complex generics, where we’re often talking about more complex analytical techniques, to both create and measure quality in those medicines, the education tools become more important. Everything from simple medicines that have been used for 70 years to biologics and everything in between, requires so much more technical sophistication for a generic manufacturer to produce a product with reliable quality.

People are sometimes overlooking the obvious answer: it’s really hard. If manufacturers do it poorly, they’ll waste a lot of money so we try to make it easier and make them better equipped to do the analytical R&D and create these new generics in the first place.

IPT: What physical components of manufacturing need to be considered when ‘genericizing’ a drug?

RP:​ We apply four lenses to any medicine, even the new wave of digital medicine. Identity: What is the medicine? Purity: What does it have that it shouldn’t have? Strength: How much of it is there? Performance: Does its dissolve? Does the medicine get into the bloodstream? We apply those four lenses to all medicine and that’s how we think about quality.

Typically, drug manufacturers don’t produce any of the precursor materials, they buy them. What comes into the factory are excipients, glues, binders, colorants, an API, also solutions and other chemical reagents to create this product.

In order to create a quality product out the back-end, not only do you have to do things right inside your factory, you have to buy the right materials and ensure they’re high quality.

USP has specific standards for the ingredients, the API, the excipients and so on. There are also guidances for how well you create the product itself based upon FDA and GMP rules, but also the quality standards USP has helps [manufacturers] do the testing to get the correct result.

IPT: How have generics affected the economy? Can generics boost the economy?

RP:​ We look at economic development as an important element of medicine quality. We have multiple offices, and do development work funded by the US government in Africa. We’re really proud of this work. It’s not all about what we do, but how do we train regulators and those in the industry how to reach our standards. In that context, if the marketplace doesn’t support purchasing of quality medicine then you’re not going to have a quality medicine supply. But, once the marketplace is having the expectation for quality and a local quality starts to meet that expectation, suddenly that local company is able to export. So, we’ve worked with manufacturers in Nigeria in partnership with WHO and they started creating these essential medicines for maternal health. Within only one year, they received WHO’s certification, which enabled them to export all throughout West Africa.

We’re working in the complex area of drug-device combinations in digital medicine, by developing quality standards we hope to build trust in the medicine sooner. People have access to those quality medicines and in the process those companies who do well, do well because they’re creating quality medicine – that’s something we’re proud of.

Ron Piervincenzi currently serves as CEO of USP. Previously he was a partner in McKinsey & Company's Global Pharmaceutical and Medical Products Practice for 12 years, where he launched McKinsey's global drug safety, medical and regulatory service line. He also served as VP in development sciences with Biogen.

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