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