Why is a Separate Manufacturing Facility Required For Penicillin And Non Penicillin Products ?

Why is a Separate Manufacturing Facility Required For Penicillin And Non Penicillin Products ?

What Is Penicillin?

Penicillins are a group of natural or semisynthetic antibiotics containing beta-lactam rings with 6 APA or 6 aminopenicillanic acid and are effective against bacteria. Penicillin was discovered by Alexander Fleming in 1928 from the fungus Penicillium notatum.

What is a Beta-Lactam Ring?

Beta-lactam is a 4 membered lactam & lactam is an amide in the form of cyclic amide. This lactam is called beta-lactam because nitrogen is attached to the beta carbon. Beta-lactam is part of many important antibiotics and these antibiotics work by inhibiting the synthesis of the cell wall of bacteria. The antibiotics those containing beta-lactam ring are known as beta-lactam antibiotics.

Name of some Antibiotics Containing Beta-Lactam Ring like Penicillin, Cephalosporin, Penams, Carbapenem, Monobactams etc.

Hypersensitivity To Penicillin

Apart from giving many useful results in treating infections, penicillin is also harmful to those individuals who are allergic or sensitive to penicillin and produce minor skin rashes to life taking anaphylactic shocks. The hypersensitivity reactions of penicillin may include the following:

• Skin Rashes
• Hay Fever
• Asthma
• Hives
• Itching Eyes
• Swelling Of Tongue
• Swelling of face
• Difficulty in breathing
• Runny nose
• Fever
• Anaphylaxis

Anaphylaxis is a life-threatening effect and it may contain many symptoms which are as follows:

• Tightening of airways resulting in difficulty of breathing,
• Nausea
• Vomiting
• Abdominal Cramps
• Fainting
• Fast or slow pulse rate
• Reduction in B.P

Penicillin allergy is observed in patients sensitive to penicillin because the immune system recognizes the penicillin drug as a bacteria or virus and starts fighting against the drug.

Why Does Penicillin Manufacturing Require a Separate Facility?

As we discussed in the above portion, penicillins are sensitizing agents and may trigger hypersensitivity reactions, although the ratio is very low as 10% but US-FDA and other regulatory bodies demand to manufacture these antibiotics in separate facilities to prevent cross-contamination.

So a common question is

“What does a separate manufacturing facility mean?

The answer is very simple:

A separate manufacturing facility is a design that has, Separate manufacturing area from the main plant for manufacturing of other products.

1. Separate HVAC System
2. Separate Equipment
3. Separate WorkForce
4. Separate Laundry
5. Separate Canteen
6. Separate Washrooms

1. Separate Manufacturing Area

To prevent cross-contamination of penicillin with non-penicillin beta-lactam antibiotics or with other general products the manufacturing plant of penicillin antibiotics is dedicated and built separately where only penicillin beta-lactam antibiotics are manufactured.

2. Separate HVAC

The separate plant built for penicillin is installed with its heating, ventilation and air conditioning system which has no connection with any other facility. It is to prevent cross-contamination and as we know that air may also result in cross-contamination so a suitable distance is maintained between penicillin and other products manufacturing plants.

The common confusing question which is asked about distance is that how much distance should we maintain between penicillin manufacturing plant & other products plant?

A rough estimation is that a distance of 75 meters or more than 75 meters should be maintained between plant to plant.

3. Separate Equipment

In penicillin plants dedicated equipment and machines are used. Never shift or transfer any machine or part from the penicillin plant to another plant because any traces left may result in triggering the hypersensitive reactions.

4. Separate Work Force

All the staff including pharmacists, workers and engineering staff are separately hired for the penicillin plant. Personnel movement from the penicillin plant to the non-penicillin beta-lactam plant is not allowed because it may result in cross-contamination.

One important point to remember is that top-level management like director production, director compliance etc should also be separated to ensure strict control.

5. Separate Laundry, Canteen & Washrooms

For washing uniforms, the laundry of penicillin is built separately. For tea, lunch & dinner the staff must have a separate canteen and in the same, we have a separate washroom facility.

Important Points

• Like penicillin for all other sensitizing non-penicillin beta-lactam antibiotic classes, the FDA recommends separate manufacturing facilities and strict controls.
• The penicillin sensitivity or hypersensitivity due to penicillin may be so severe that the invisible traces of penicillin on the documents like BMRs can start hypersensitivity reactions.
• Sometimes it may be the case where a plant is not manufacturing the penicillin or other non-penicillin beta-lactam antibiotics but the adjacent or nearby plant is producing the above-mentioned.
• So preventive measures will have to be taken by the plant of non-penicillin to prevent penicillin hypersensitivity.

• Some Important Antibiotics Side Effects
• Classes of Antibiotics and their Spectrum of Activity
• Timeline of Antibiotics