The document summarizes international and national challenges pertaining to generic drugs. For international challenges, it provides examples of generic drug recalls due to containing undeclared active ingredients, incorrect drug strengths leading to overdoses, and dissolution failures reducing drug effectiveness. For national challenges, it analyzes examples of non-approved drug formulations and dosage forms in Pakistan that could impact bioavailability, stability, and safety. The conclusion emphasizes the importance of only approving generic drugs with formulations and strengths supported by evidence from reference drug regulatory agencies.

1. Pharmaceutical Manufacturing
Generic Drug;
International & National Challenges
Faheem Lakhani
Plant Manager, Platinum Pharmaceuticals.

2. Flow of Presentation
• Concept of Generic Drug
• Challenges pertaining to Generic Drugs
• International
• National
• Take Home Massage

3. Generic Drug
A pharmaceutical drug, equivalent to a brand name product in:
• Dosage
• Strength
• Route of administration
• Quality
• Performance
• And intended use
Must contain the same active ingredient as the original brand name formulation.

4. International Challenges Pertaining
to Generic Drug
International Cases

5. Case#1: Digoxin tab
• Manufactured in New jersey by the Actavis group
• Product recalled due to strength of tab…greater than
labeled …a potentially lethal overdose, caused heart
failure.
• Dose of Digoxin has to be just right

6. Case#2: Caverflo natural herbal Coffee
• Presence of undeclared active ingredients (Sildanafil, Tadelafil
& undeclared milk).
• Ingredient may interact with nitrates in some prescription
drug, such as nitroglycerin , and may lower blood pressure to
dangerous levels.
• People having allergy or severe sensitivity to milk.

7. Case#3: Paliperidone extended release Tab
• Teva Pharma…for the treatment of Schizophrenia
•
• Dissolution failure could reduce effectiveness in treating a
patient’s mental and /or mood symptoms, including suicidal
thought and behavior, mental hospitalizations, aggressive
behavior.

8. Case#4: Piyanping Anti-Itch Lotion
• The product was manufactured using the active pharmaceutical
ingredient dexamethasone rather than hydrocortisone.
• Effecting Adrenal suppression,( high blood sugar , weakened
immunity, electrolyte imbalances, slowing of growth in children)

9. Case#5: Venlafaxine
• Anti depressant drug
• 3 lots of venlafaxine XR were recalled due to all three lots were
run on the same packaging line.
• Approx. 160,000 bottle were recalled
• Tikosyn ( a medicine use to treat heart arrhythmias) was found
in an Venlafaxine XR bottle.

10. National Challenges Pertaining to
Generic Drug
Sorry ! We Don’t have any Recalls

11. Case#1: Co-Plavix; Antiplatelet Drug
• Innovator drug available worldwide as Clopidogrel with Aspirin
as immediate release film coated tablet with bilayer tablet.
• Taking enough medicine to prevent clots…important.
• Pakistani product…. available in tablet in tablet with Aspirin as
Enteric coat and Clopidogrel as immediate release.
Bilayer Tablet in Tablet

12. Case#2: Montelukast Sodium 10mg Chewables
Only 10mg film coated tablets as approved by ref agencies.
May impact:
1. Bioavailability
2. Drug dissolution Profile
3. Clinical and Safety studies

13. Case#3: Montelukast sodium 5mg/5ml DP
• The innovators instructions for administrations are as follows:
“The packet should not be opened until ready to use. After opening the
packet, the full dose (with or without mixing with baby formula, breast milk, or
food ) must be administered within 15 minutes. If mixed , SINGULAIR oral
granules must not be stored for future use. Discard any unused portion.
SINGULAIR oral granules are not intended to be dissolved in any liquid
other than baby formula or breast milk for administration.

14. Case#4: Isotretinoin 20mg Hard Gelatin Cap.
• Isotretinoin degrades when exposed to light or atmospheric
oxygen.
• Batches of drug substance are stored under argon and protected
from light. Therefore, a powder filled hard gelatin capsule or
tablet dosage form may not be stable.

15. Case#5: Levofloxacin 125MG/5ML DPS
• Drug is available only in USFDA in the form of Oral Solution, 25
mg/mL.
• Multi-use self-preserving aqueous solution of levofloxacin with
pH ranging from 5.0 to 6.0.
• The appearance of Levofloxacin Oral Solution may range from
clear yellow to clear greenish-yellow. This does not adversely
affect product potency.
(Ref: US FDA)

16. Case#6: Rabeprazole 20 Mg CAP.
• Rabeprazole (as 20mg..Sodium enteric coated pellets)
• Not available in reference drug regulatory agencies. Tablet
dosage forms are available.
• May impact:
1. Bioavailability
2. Drug dissolution Profile
3. Clinical and Safety studies

17. Case#7: Orlistat 60MG CAPS.
• Xenical is presented as a conventional hard gelatin
capsule (size 1) containing pellets with an active
substance concentration of 50%.

18. Case#8: Famotidine 40 MG/5ML Sus.
• Not approved by reference drug regulatory agencies.
• Internationally available formulation is dry powder for
suspension in the strength of 40 mg/ 5 ml.

19. TakeHome
Massage

20. Thank you