Generics, Biosimilars and Interchangeables
license numbers
FDA gives the biologics a number and it must be on the label
are highly similar and interchangeable the same thing
NO
biosimilar indications
may be approved for an indication without direct studies of the biosimilar in that indication if total evidence supports administration for at least one of the RP indications then the manufacturer can use data and info to justify approval for other indications
are adalat and procardia the same generic
depends on the formulation, release but they both are nifedipine
CDER CBER
depends on what the product is public health service
suffix should
have no meaning be four lowercase letters, 3 are distinct nonproprietary be attached to core with hyphen be free of legal barriers that would restrict usage
types of generic substitution regulations
mandatory permissive
biologic patent protection
manufacturers of innovator biologics are granted 12 years exclusivity + 6 mo if pediatric product applications may not be submitted for 4 years after approval first interchangeable is 1 year exclusivity
BLA must
meet product and facility standards inspection of facility and process
how many molecules have launched from this, how many biosimilars
11 22
NDA goes through
FDA for approval
biosimilar biologic product
- demonstrates that the product is highly similar to the RP by extensively analyzing the structure and function of both the RP and the proposed biosimilar - demonstrates that the biosimilar has no clinically meaningful differences from the RP in terms of safety, purity and potency
categories of therapeutic biological products regulated by CDER
1. MABs for in vivo use 2. most proteins for therapeutic use including cytokines, enzymes and other novel proteins except those specifically assigned to CBER 3. immunomodulators 4. growth factors, cytokines, and mab intended to mobilize, stimulate, decrease or alter the production of hematopoietic cells in vivo
how many biosimilar approvals are there across how many molecules
33 13
how many states have biosimilar legislation
47 OK, MS, DC
Sally, a pharmacist at SuperClinic Pharmacy, received a prescription from a patient, Mr. Lee, for Menton. Mr. Lee asked if there was a less expensive generic drug available because he had to pay for his medications personally. Sally knew that there was a generic product available but that it had a B rating to Menton in the FDA's Orange Book. What does it mean that Menton has a B rating and why?
If the state and physician allowed it we could but we would also be liable for it
351k is for
a generic
the concept of extrapolation is based on
all available data and information in the biosimilar application FDA previous finding of safety and efficacy for other approved indications for the reference product knowledge and consideration of various scientific factors for each indication
biosimilar insulins approved
basaglar-- lantus admelog---humalog
suffix should not
be false or misleading include numerals and other symbols have abbreviations that could cause misinterpretation contain or suggest any drug name or core name look similar to the name of a currently marketed product look similar to the name of license holder be too similar to any other FDA designated nonproprietary name suffix
PHS Act and manufacturing
because of the complexity of manufacturing and characterizing they emphasize the importance of appropriate manufacturing control for products environment, manufacturing systems
what is the most prescribed biosimilar
bevacaziumab, avastin
biosimilar
biological product that is highly similar to and has no clinically meaningful differences from an existing FDA approved reference product
PHS act 351(a)
biological products are licensed under this
interchangeable
can be substituted without intervention of prescriber biosimilar that produces the same clinical result as the RP in any patient and it is administered more than once to an individual with a risk in terms of safety or diminished efficacy of alternating or switching between use of the product and the RP is not greater than the risk of using the RP without such alteration or swtich
what causes the biologic product to change
changes in manufacturing process, equipment, or facilities could change it which could require additional clinical studies
name some NTI drugs
clonidine, warfarin, levothyroxine, phenytoin, carbamazepine, lithium carbonate, minoxidil
pharmaceutical equivalence
contain same active ingredient identical in strength dosage form
naming for biologics
core name + suffix can add prefix
reference standard
drug product selected by FDA that an applicant seeking approval of an ANDA must use in conducting an in vivo bioequivalence study required for approval
biological products are subsets of ____ and are regulated under
drugs FDCA
narrow therapeutic index drugs
drugs with less than a 2 fold difference between median lethal dose and median effective dose or two fold difference between MTC and MEC
Hatch-Waxman amendment of FDCA
evaluates pharmaceutically equivalent products on the basis of bioequivalence
Drug Price Competition and Patent Term Restoration Act of 1984
generic drugs must demonstrate proof of bioequivalence to a reference standard before approval
orange book
has approved drug products uses 2 letter rating system and could be 2 letters and a number
Change from FDCA to PHS Act
insulin, human growth hormone, pancrelipase, chorionic gonadotropin, follitropin and menotropins were moved from being regulated by FDCA to the PHS
can you identify the identity of the active component in a biologics
it's very difficult so they are defined by manufacturing
biologics path to approval
lab testing --> animal trials --> clinical trials under IND --> product safe and effective submit a BLA --> FDA approval biologics license with a US license number
why are biologics hard to replicate
large, complex molecules dependent on living systems
purple book
list biological products, biosimilar, interchangeables licensed under PHS act has date it was licensed under 351(a) and whether it was evaluated for RP exclusivity under 351(k)(7) if product was licensed under 351(k)
reference listed drug
listed drug identified by FDA as the drug product upon which an applicant relies in seeking approval of its ANDA
The prescription was written for lisinopril 10mg. The pharmacist filled the medication with lisinopril 10mg from Mylan Pharmaceuticals but labeled the medication as Zestril for a Medicaid patient. The pharmacist was audited by the Board. The Board of Pharmacy cited the pharmacist for what violations?
mislabeled, misbranded, billed medicaid for a brand and gave generic
labeling requirements for generics
must accurately differentiate generic product from brand
mandatory
must substitute a less expensive generic unless DAW
351a is for a
new drug
are there any current interchanges approved
no
is therapeutic equivalence the same as therapeutic substitution
no
does the FDA have authority over substitution
no run by pharmacy practice act
do biosimilars have all indications
no so need to know when you might use
BCPIA- 42 USC 262(k)
part of the ACA with the intent to reduce cost of specialty products by creating abbreviated licensure pathway for biosimilars PHS Act 351 (k)
therapeutically equivalent
pharmaceutical equivalents that are bioequivalent acceptable manufacturing methods and control procedures
permissive
pharmacist may choose to substitute if the prescriber issues Rx allowing substitution
premarin issues
problems with generic who tried to challenge the patent because they would have difficulty due to the conjugated estrogens we do not know which estrogen caused the effect
AB rated products
products meets necessary bioequivalence requirements and may be substituted if equivalency problem resolved by in vivo or in vitro studies
B rated products
products that are not bioequivalent
what is the book for biological products
purple book
BLA must abide by
regulations, guidance document, PDUFA
bioequivalent products
safe and effective as innovator product same clinical safety and efficacy
reference product
single biological product already approved by FDA a biosimilar is compared to this
requirements for generic substitution
some states mandate consumer consent, require cost saving be passed on to the consumer prescription drug coverage may impact cost to consumer
how can prescriber prevent substitution
state dispense as written or brand medically necessary
who decides biosimilar substitution
states most require interchangeability
therapeutic substitution vs therapeutic equivalence
substitution is when the drug is the same category-- happens a lot in hospitals lisinopril sub for enalapril
a 351(k) BLA must include information showing that
the product is a biosimilar to 1 reference product the product and the RP have the same MOA for the proposed conditions of use but only to the extent the mechanisms are known for RP conditions of use in labeling have been previously approved route of admin, dosage form, strength are the same facility in which the proposed product is manufactured, processed, packed or held meets standards designed to assure that the biological product continues to be safe, pure and potent
Section 505 of FDCA
therapeutic protein products are approved under this
A rated products
therapeutically equivalent to brand name/reference product
extrapolation
use data to support other indications critical to abbreviated pathway to improve access and lower cost
should pharmacists substitute B rated NTI drugs
use judgement
biologics
virus, therapeutic serum, toxin, antitoxin, vaccine, blood, blood component or derivative, allergenic product or analogous product applicable to the prevention, treatment or cure of a disease or condition of human beings
if the medication is written generically can brand be dispensed
yes