SAS 1 EXAM 3 JP

Pure Food and Drug Act 1906

Truth in labeling and no adulteration/misbranding of food & drugs

Food and Drug Cosmetic Act 1938 (FD&C Act)

No new drug can be approved until proven safe by the FDA

Drug

1. Recognized officially

2. Intended for therapy

3. Intended to affect structure/function of body

Cosmetics

1. Intended to be topical products for a certain change

2. Does NOT include soap

Can become a drug IF the seller makes a health function claim (should comply w/ FD&C Act)

eg) fluoride toothpaste, anti-dandruff shampoo, some sunscreens

Deivce

An instrument that is…

1. Recognized officially

2. Intended for therapeutic effects

3. Affects the structure of the human/animal body

DOES NOT achieve the intended purpose by chemical action & metabolism

Approved drugs and new drugs

• addition of new substance

• new combination of approved drugs

• change in proportion of ingredients

• new intended use

• dosage, method, or duration of administration or application is changed

NDA

• collects evidence that drug is safe and effective obtained from animal and clinical studies

• to collect these studies, the sponsor must file an IND

IND

• requires substantial information about the drug

• drug must be safe AND effective in animals trials

• required before clinical trial may begin

Informed consent

• REQUIRED in patient participation in phase I, II, III

• must be in writing for phase I & II trials

National Drug Code (NDC)

NDC 0777-3106-02

First four (0777)= labeler code (pfizer)

Second four (3106)= product code (advil)

Last two (02)= package code (24 tablets one bottle)

Durham-Humphrey Amendment 1951

Authorized the FDA to classify drugs as prescription only vs OTC

Kefauver-Harris Amendment 1962

• Required evidence of effectiveness

• Established GMP requirement

• Strengthened clinical trials by requiring informed consent & adverse drug reporting

Drug Efficacy Study Implementation (DESI) of 1968

• US supreme court: generic drugs are new drugs & subject to FDA approval

• Following the Keauver-Harris Amendment

• DESI expert panels individually evaluate prescription drugs’ efficacy

Efficacy Review of OTC Drugs- Category I

Generally recognized as safe and effective

Efficacy Review of OTC Drugs- Category II

Not generally recognized as safe and effective and/or misbranded

Efficacy Review of OTC Drugs- Category III

Insufficient data available

Hatch-Waxman Amendment (1984)

• aka “the drug price competition & patent term restoration act”

• created a statutory generic drug approval process

• generics no longer had to repeat full clinical trials

• established the abbreviated new drug applications process (ANDA)

Abbreviated New Drug Applications (ANDA)

Generic drug companies must establish that the generic drug is effectively a duplicate of the branded NDA drug

Orange book

approved human drug products

Purple book

Human biologics

Green book

Veterinary drugs

Label

Matter physically written on the immediate container

Labeling

All labels & all other written, printed or graphic matter

Adequate directions for use

Under which the layman can use a drug safely and for the purposes for which it is intended.
On: OTC Drug Facts label

Adequate information for use

Clinical information a practitioner needs to prescribe or use the drug safely, including indications, dosing, contraindications, and warnings.

On: Prescription prescribing information

Pregnancy & Lactation Labeling Rule (PLLR)

FDA removed letter grades

• Drugs approved after 6/30/2015

  • Required to adopt PLLR immediately

• Drugs approved 6/30/2001- 6/30/2015

  • Required to transition to PLLR, but updates occurred on a delayed schedule

• Drugs approved before 6/30/2001

  • May still show letter categories

OTC not subject to PLLR

Required PLLR Sections: pregnancy, lactation, and females & males of reproductive potential

Black Box Warning

• labeling requirement that FDA may impose if the drug carries a risk of death or serious injury

• NOT a contradiction

Food and Drug Administration Amendments Act of 2007 (FDAAA)

• gave FDA authority to require manufacturers to add safety information or warning post-market approval

• required FDA to develop and maintain website guidance documents

• established “Sentinel Initiative” designed to detect early signs of a drug’s risk

• granted the FDA authority to require REMs as a condition for approval of an NDA or post-market

Risk Evaluation Mitigation Strategy (REMS)

• FDAA gives FAA authority to require a drug product sponsor to establish special procedures directed at patient safety

• Intended to manage known/potential serious risks of the product

Patient Package Inserts (PPI)

• FDA approved patient labeling developed/ manufactured by FDA

• Required to be dispensed w/ oral contraceptives & estrogen containing products

Medication Guide

• FDA approved patient handouts required for certain prescription medications

• must be given each time medication is dispensed when required by labeling OR as a part of REMs

eg) opioids, antiepileptics (lamotrigine, lacosamide), antidepressants & antipsychotics, etc.

Poison Prevention Packaging Act (PPPA)

• Child resistant packaging for home-use oral meds, unless the medication is exempt or a waiver is filed

Patient Waiver= may be blanket

Practitioner Waiver= covers that prescription only

PPPA Exemptions

Drug Recalls

How recalls occur

• Voluntary action by the manufacturer

• FDA request

• FDA mandated recall

FDA Mandatory Recall Authority Applies Only To:

• infant formula

• medical devices

• biological products

• tobacco products

Drug Recall Classes

Recall Classes:
I: Serious adverse health effects or death
II: Temporary or medically reverisble effectsl serious effects remote
III: Unlikely to cause adverse health effect

Market withdrawal: product with minor violation removed from 2

Adulteration

Containing poisonous, insanity ingredients or manufactured without adequate controls

eg) contains poisonous, deleterious, filthy, putrid, decomposed products. prepared under unsanitary conditions. unsafe color additives (hair dyes that contain coal tar are EXEMPT)

Misbranded Drugs

• FDA approves the exact wording of the label and labeling during the pre-market approval process

• “representations made by the manufacturer on the label/labeling

• false or misleading labels

• imitation of another drug

• its packaging does not conform

• label is not prominently displayed

Schedule II

• High abuse potential

• Acceptable medical use

• Abuse may lead to severe physical / psychological dependence

Schedule III

• Potential of abuse CII controlled substances

• Currently acceptable medical treatment in the US

• Abuse may lead to moderate or low physical dependence or high psychological dependence

• 1.8g of codeine or dihydrocodeine per 100 mL or not more than 90 mg per dosage unit

Schedule IV

• Low potential of abuse relative to CIII controlled substance

• Current acceptable medical treatment in the US

• Abuse may lead to limited physical dependence or high psychological dependence relative to CIII controlled substances

Schedule V

• Little abuse potential

• Current acceptable medical treatment in the US

• Abuse may lead to limited physical dependence or high psychological dependence relative to CIV controlled substances

Schedule VI - MA

a controlled substance schedule for prescription drugs that are not otherwise scheduled as CI- CV

• consists of all prescription drugs

• includes Rx Only

Commercial containers

All commercial containers of drugs in schedule I-V must bear a symbol fo CS schedule it has been assigned to

Prescription container

A clear, concise warning that it is a crime to transfer the drug to any person other than the patient

Controlled substance registration: renewal requirements

• manufacturers/ distributors= renew annually

• dispenser: renew every 3 years

Controlled substance registration: Registration Exemptions

• agents or employees of a registered entity

• common carriers/ warehousemen

• ultimate users

Individual practitioners as agents or employees

Individual practitioner = physician, dentist, vet, or other licensed professional authorized to dispense CS

agents/ employees may administer or dispense but may NOT prescribe under another practitioner’s DEA registration

DEA Number

DEA Number Check Validity

DEA Forms: DEA 224/225

Application for CS registration (dispensers)/(manufacturers, distributors, NTPs)
APPLY

DEA Forms: DEA 223

CERTIFICATE of registration (CII-CV) issued after approval

DEA Forms: DEA 222/CSOS

Paper order form for Schedule I & II / electronic ordering system for schedule I & II
ORDER

DEA Forms: DEA 106

Report of significant loss or suspected/actual theft
LOSS/THEFT

DEA Forms: DEA 41

DESTRUCTION

Pharmacy inspections

Federal (DEA)= need warrant or consent
Massachusetts (State)= no warrant and no prior notice

Controlled substances: security requirements

Registrants must maintain effective controls and procedures to prevent theft and diversion of controlled substances

• in pharmacy security questions, look for red flags in access, storage locks, or alarms

Prescribing under a hospital’s DEA registration (interns, residents, employees)

The hospital must assign a specific internal code number to each authorized practitioner

• The code is a suffix to the hospital’s DEA registration

  • APO123456-A12

• Practitioners may prescribe under a hospital’s DEA registration only if all conditions are met, and the practitioner is assigned an internal code that appears as a suffix to the hospital’s DEA number

Controlled substances: record keep requirements

Federal

• CS must be kept at least 2 years

• readily retrievable

• be available for inspection and copying by DEA

• all registrants

Massachusetts

• follows 2 year retention

• exception: defective product logs must be kept 10 yers

Controlled substances: inventory requirements

Federal requirements:

• complete and accurate list of all controlled substances

• kept at the registered location, readily retrievable, for 2 years

• CII inventory must be kept separate from all other controlled substances

• CII: actual physical count

• CIII-CIV: estimated count unless container >1,000 tablets/capsules, then exact count

Controlled substances: Requirements of inventories

Initial inventory

• Taken when DEA registration is issued

• Actual physical count of all controlled substances

• If none on hand —> record zero inventory

Biennial Inventory (Federal + Massachusetts)

• Required every 2 years

• May be taken on any date within 2 years

• Must be kept on file (not submitted to DEA)

Perpetual Inventory (Massachusetts)

• Required for all Schedule II

• Tracks received, dispensed, disposed

• Must be reconciled at least every 10 days

Ordering Controlled: CI & CII

DEA Form 222

• Required for each distribution, purchase, or transfer of Schedule I or II

• Lost or stolen 222 form

  • Notify DEA in writing

CSOS (Electronic Orders)

• Electronic equivalent to Form 222 CSOS order may NOT be filled is:

  • certificate is expired or revoked

  • validation shows the order is defective or invalid for any reason

  • if any of the above occur —> unaccepted/defective electronic order

Power of Attorney

A registrant may authorize one or more individuals to sign DEA Form 222 or CSOS orders on the registrant’s behalf by executing a Power of Attorney (POA)
Who may grant POA: the registrant
- Individual (owner)
- Partner (if partnership)
- Corporate officer

Ordering Controlled Substances: III-V

Recordkeeping Requirement:

• must be readily retrievable for DEA inspection

• retained for 2 years (federal +masschusetts)

Controlled substances: lost or theft

Federal

• Notify DEA Field Division Office in writing within 1 business day

• File DEA Form 106

Massachusetts

• Report within 24 hours of discovery

• If licensed by DCP —> file drug incident report with the DrugControl Program

• If licensed by the Board of Pharmacy —> reoprt under board policy 16-02

DEA Pharmacist’s Manual Destruction/Disposal

CII Transfers

• Reverse distributor must issue an official order form (DEA Form 222, CSOS)

CIII-CV Transfers

• Pharmacy must maintain a record of distribution

Reverse distributor complete and files DEA Form 41

• Pharmacy does not file form 41

  • only mains documentation of the transfer with CS records

Opioid Treatment Programs (OTPs)

• provides methadone and buprenorphine for detoxification and maintenance

• Methadone

  • May NOT be prescribed or dispensed for detoxification or maintenance outside of an Opioid Treatment Program (OTP)

  • Retail pharmacies may dispense methadone only for pain management

  • CANNOT be prescribed for OUD outside an OTP

  • Pharmacies may NOT dispense for OUD

• Buprenorphine

  • May be prescribed and dispensed for OUD outside of OTP

  • Pharmacies may dispense for OUD

Detoxification

• giving decreasing doses to reach a narcotic-free state

Short-Term Detoxification= ≤30 days

Long-Term Detoxification= ≥30 days but ≤180 days

Maintenance

Dispensing narcotic drugs for >21 days to treat dependence on heroin or other morphine-like drugs

Combat Methamphetamine Epidemic Act (CMEA) of 2005 & Metamphetamine Act of 2008

• Ephedrine, Pseudoephedrine (PSE), Phenylpropanolamine (PPA)= classified as “schedule listed chemical products” federally

• Retail purchase limits

  • 3.6 grams per day

  • 9 grams per 30 days (monthly limit)

    • Import limit: no more than 7.5 grams (of the 9-gram monthly limit) may be imported via private/comercial carrier or postal service

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