Generic Safety Labeling: FDA’s new regulation – Part 2

Nov 20, 2013

Pharmacovigilance, Drug Safety and Regulatory Affairs Author & Expert

In Part 1 we looked at the old and the proposed new regulation on generic labeling.  Now we will take a look at possible implications.

Comments and Implications

The new regulation will change the landscape for all the stakeholders.

Branded Companies

For branded companies there will be good and bad points.

  • Routine PV and legalities become more complex .
    • The PV for these “old” drugs will get more complex as the drug safety unit will now have to follow at the very least the FDA generic label change website.  This will require more people and will increase costs.
    • They may also want to routinely monitor the actual labels of each generic.
    • Drug safety groups will have to pay far more attention to tracking down the actual manufacturers of generics when doing follow up on cases.
    • They may wish to periodically obtain from FOI, the SAE cases of the generics from the FDA’s FAERS database to avoid “surprises”.
    • If the branded company sells both the brand and generic of the same product, the company may wish to consider closing or selling the branded NDA if its maintenance now becomes too expensive or time consuming.  They may find it preferable to sell only the generic version.
    • In tracking down individual SAEs, the company may want to make much greater efforts to determine the generic manufacturer to attribute the case to that drug/company.  When the manufacturer is unknown the branded company receives the case, they must process it as if it were theirs indicating the manufacturer is unknown.
    • The branded company will have to track and inform all generic houses of label changes submitted.  This may actually help the brand company if they choose to make multiple tactical changes to the label forcing the generic houses to continually change their label.  On a unit cost basis this is probably easier and cheaper for the branded company than for the (understaffed) generic house.
    • Liability issues may become more complex also.  If the branded label is not rapidly changed there may be more risk of lawsuits.  The issue of how long the divergences between and amongst the labels will last is unclear.  One can imagine the plaintiff’s bar attacking a company if it is weeks to months “late” in changing its label and producing harm in patients.
    • The branded company may have to work more closely with their generic competitors especially if a REMS is in place.
    • The branded company may be “happy” to send many cases to the generic house for them to work up, database etc.

Generic Companies

To a certain degree, the “free ride” is over.   The generics will lose their “anonymity”.

  • Generic houses often spend little time, money or energy on regulatory matters, drug safety and PV.  If the public now starts paying attention to who the generic manufacturer is there may be more reporting spontaneous SAEs/AEs.  The companies may need to set up a formal PV department, out-source the function, get a safety database etc.
  • If physicians, pharmacists and the public start paying attention to which generics they are dispensed, there may be more SAE reporting of generics.
  • Users and prescribers may now want to avoid those generics coming from certain countries or companies which have had bad FDA GMP factory inspections.
  • There may be competition amongst generics on issues other than price.
  • Generic houses will now clearly have more liability and may be sued more easily and frequently.
  • Generic products may start competing: Don’t use generic X since their factory in India/China was shut down by FDA etc.
  • Costs for generics may rise without the increase going to the generic companies’ bottom line (that is, costs up, profit down).
  • These requirements are now a new barrier to entry into the market for generics. This may lead to fewer generics and higher costs which is probably not the intent of this new regulation.
  • Much more attention will now have to be paid to ensure that the very latest label is now supplied with the drug shipped to pharmacies, wholesalers, patients, hospitals etc.
  • It may be worthwhile detailing generic drugs now creating more “branded generics”.  New avenues of marketing and selling will arise.
  • On the up side for the public, there will need to be more attention paid by the generic houses to the supply chain and quality of the product.

The Lawyers

More lawsuits! More work and income for both the plaintiff and the defender bars.

  • As generic houses really could not be successfully sued until now, a whole new area of litigation opens up.  Not just harm to the patient but the added risk of failing to warn by delaying changing the label for the prescriber and the user.
  • It will probably pay for some law firms to carefully monitor all generic labels and see which ones are late in changing their labels.


  • Physicians and other prescribers may now have to pay more attention to which generics their patients are prescribed.
  • What this probably will boil down to is a list of “trusted” generic companies.
  • Prescribers may now write for a particular brand of generic or may write that a particular generic brand NOT be dispensed.
  • Whether physician liability and the “learned intermediary” concept will change based on this is unclear.  It simply may become more time-consuming and risky to the prescriber to prescribe a generic – any generic.  The prescriber may then totally avoid all generics or simply prescribe one “trusted” generic without having to follow labeling on all of them.

The Patients

  • Generics will not be so simple anymore.  There will be differences and consumers may realize that not all products are the same.  The effects and risks may be different. 
  • It may not be a good thing to switch to a new generic each time a patient refills his or her prescription.  It may be better to stick to the same generic.

The Internet & Social Media

  • We will surely see some smartphone apps devoted to helping the patients and the prescribers check which generics are “better” and which labels are up to date.
  • Some folks may start tracking which labels are up to date and which are not and providing (or selling) this information.


  • Lots more work for FDA.  There are a lot of generics out there and the choreography of the label changes, the web postings, the unintended consequences and such will complicate matters.
  • Consumers, physicians and reporters may find it is easier to report SAEs to FDA at MedWatch than trying to track down the phone number or website of a generic manufacturer.  The vast majority of spontaneous cases are now reported to sponsors and NDA/ANDA holders.  This balance may change.


  • Pharmacy chains may want to find one generic “brand” and stick with it rather than changing vendors and getting a different generic each time they reorder their stock.  Competition may be less focused on price.

 The Drugs Themselves

  • People may start to pay more attention to generic drugs themselves.  It may become evident that not all generics are therapeutically equivalent even if the active ingredient is the same.  We may see that excipients, fillers, manufacturing processes and other technical issues alter the effects of the drugs.
  • We may see that those generics with wide specifications for, say, dose range in tablets or capsules (e.g. 85%-115% such that a 100mg tablet might contain anywhere from 85 to 115 mg of the active ingredient) will produce different safety profiles when a patient switches from one company’s generic to another.  That is, the first generic tablet delivered 85 mg of the active and the refill, from another generic company, delivers 115 mg per tablet – a 35% increase in dose delivered.
  • More attention will have to be paid to the supply chain and the quality of manufacture.
  • It may become worthwhile to manufacture drugs in the US, Canada, the EU and other areas which, arguably, have higher quality standards.


Firstly, I think FDA should rethink the concept of “equivalence”.  A generic drug is not exactly the same as the branded drug.  I’d separate the equivalence concept in to efficacy/effectiveness and safety.

It’s likely though not always certain that a small molecule generic drug if delivered in the same way, amount, dose etc. will work the same in the patient as the branded drug.  There will be differences presumably based on excipients, fillers, how tightly the tablet was packed, manufactured etc.

Safety, however, may actually differ from the branded product.  There are different vendors supplying different excipients, fillers, packing machines etc.  So I would propose that the different generics may each have slightly different safety profiles and that there is no reason to presume the safety profile will be exactly the same as the branded drug or any other generic.  So why force the labels to coincide?  Let each drug develop it’s own safety profile.  There should be the equivalent of “class labeling” for some safety issues that clearly transcend the different manufacturer and are due to the active moiety or the delivery system (e.g. injections) or whatever. Don’t artificially force parity where it may not exist.

To this end, FDA should simplify what sounds like a very complex and painful process.

So this is an early posting after the draft regulation is published.  I suspect we will see a lot of comments and the final regulation may be somewhat different.  I also suspect the FDA is under a lot of pressure to get this finalized by mid-2014. Stay tuned.

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