Manufacturing units in

hospitalsHospital Pharmacy Seminar

Hospital manufacturing units

Hospital manufacturing units The manufacture of medicines is a complex operation

and must conform to GMP requirements of the MCA. These require a system of QA designed to build quality into each product at all stages of its manufacture. To this end, pharmaceutical QA services work closely with production staff and provide a series of checks, tests and controls throughout the manufacturing process as follows: Microbiological and chemical testing where appropriate

of ingredients, labels and packaging components, in-process samples and finished products.

Checking and approval of all standard operating procedures and production documents.

Environmental monitoring in clean and aseptic areas.

Hospital manufacturing units

Validating processes, equipment and procedures. Monitoring the performance of sterilizers. Pharmaceutical development work, including

formulation development, stability studies and manufacturing and analytical method development and validation.

Planned quality auditing at regular intervals. Liaison with the MCA.

Hospital manufacturing units Each manufacturing unit is required to be licensed

under the Medicines Act, holding a manufacturer’s specials license.

A requirement of the license is that there must be a named production manager and named quality controller for the release for use of all products manufactured in the unity.

This is a key role for QA pharmacists and other appropriately qualified and experienced QA staff.

Hospital manufacturing units Before releasing each batch for use, the quality

controller has to satisfy him-/herself that GMP, as laid down in MCA guidance, has been complied with, that all manufacturing and QC processes have been validated, that all checks and tests have been carried out and are satisfactory.

That all documentation is satisfactory, and that all other factors which affect the product quality are satisfactory. This requires highly trained and competent QC staff who are fully aware of the quality, safety, and efficacy requirements of pharmaceutical products.

Pharmacy manufacturing unitsTotal Parenteral Nutrition (TPN), Chemotherapy and Extemporaneous Preparations

Pharmacy manufacturing units The Pharmacy manufacturing units are involved in

the preparation of medicines that are not available commercially in a ready-to-use format.

The majority of this work is concerned with aseptic preparation.

This is the preparation and supply of products that must be completely sterile before administration to the patient.

Pharmacy manufacturing units In order for this to be achieved they are made

within special isolators which are supplied with filtered air.

The majority of aseptically prepared items are either Total Parenteral Nutrition (TPN) or chemotherapy.

Total Parenteral Nutrition (TPN)

These contain all the essential nutrients to sustain a patient if they are unable to eat food in the normal way.

TPN bags containing carbohydrates, fats and salts in a 1.5 litre formulation are purchased.

These standard bags then have vitamins, trace elements and extra minerals added as necessary.

Chemotherapy

Chemotherapy

Cytotoxic drugs are used in the treatment of cancer.

They are supplied in a ready-to-use form to the ward which means that staff are not exposed to the toxic nature of the medicine.

By working within the controlled environment of the aseptic suite the pharmacy operators are also protected whilst preparing the medication.

A variety of devices are made (5-Fu Walkmeds / Accufusors) which means patients are able to complete chemotherapy at home, without a stay in hospital.

Extemporaneous Preparations

Extemporaneous Preparations Whilst most medicines are commercially available,

some dosage forms cannot be purchased from large companies.

Extemporaneous preparation describes the work involved in supplying a medicine in a form or dose that is not otherwise available.

Extemporaneous Preparations The technical services departments across both

sites are involved in the manufacture of:1. Liquid formulations2. Eye drops3. Creams4. Ointments5. Quality Control

Extemporaneous Preparations Deals with all aspects of quality control within the

pharmacy manufacturing and purchasing sections. Advice is given on COSHH (control of substances

hazardous to health), medical gases and complaints regarding faulty drug products and sundries.

Dialysis solutions

Dialysis solutions

1. Peritoneal dialysis solutions: These are sterile solutions

injected into the abdominal cavity, left for 30-90 min. to allow exchange between the solution and the viscera through the visceral wall which acts as a semipermeable membrane and then they are withdrawn.

Dialysis solutions

1. Peritoneal dialysis solutions: These are used to remove toxins from the body or to

accelerate the excretory function of the kidney in cases of acute renal insufficiency.

These solutions contain glucose and electrolytes.

Dialysis solutions

2. Hemodialysis solutions: Used in severe cases of renal failure. Here, the blood leaves the body from an artery

through a polyethylene catheter into a dialyzing cell in which exchange occurs between the blood and the dialysis solution through a semi-permeable membrane to clean the blood from wastes, then the blood enters the body through a vein.

Time of passage should not exceed the clotting time [4-6 hours]

Hemodialysis solutions contain: electrolytes, preservatives, accelerators and glucose (to act as a pumping system by rendering the solution hyperosmotic)

Dialysis solutions

Diagram of Hemodialysis set

Sterilization

Sterilization

Sterilization (or sterilisation) is a term referring to any process that eliminates (removes) or kills (deactivates) all forms of life and other biological agents, including transmissible agents (such as fungi, bacteria, viruses, prions, spore forms, etc.) present in a specified region, such as a surface, a volume of fluid, medication, or in a compound such as biological culture media.

Sterilization can be achieved with one or more of the following: heat, chemicals, irradiation, high pressure, and filtration.

Sterilization

Sterilization is distinct from disinfection, sanitization, and pasteurization in that sterilization kills, deactivates, or eliminates all forms of life and other biological agents

In general, surgical instruments and medications that enter an already aseptic part of the body (such as the bloodstream, or penetrating the skin) must be sterile.

Examples of such instruments include scalpels, hypodermic needles and artificial pacemakers.

Sterilization

This is also essential in the manufacture of parenteral pharmaceuticals.

Preparation of injectable medications and intravenous solutions for fluid replacement therapy requires not only sterility but also well-designed containers to prevent entry of adventitious agents after initial product sterilization.

Blood Banks

Blood Banks

A blood bank is a cache or bank of blood or blood components, gathered as a result of blood donation or collection, stored and preserved for later use in blood transfusion.

The term "blood bank" typically refers to a division of a hospital where the storage of blood product occurs and where proper testing is performed (to reduce the risk of transfusion related adverse events).

However, it sometimes refers to a collection center, and indeed some hospitals also perform collection.

Blood products

A. Concentrates of platelets and white blood corpusclesMethod of preparation:

Blood (fresh) low speed centrifugation RBCS sediments + White blood corpuscles platelets in plasma.

Plasma (WBC. and platelets) High speed centrifugation Concentrated platelets in plasma.

Uses: Treatment of patients with leukemia

Storage: This packed in disposable plastic blood bags or

suitable glass bottles

B. Concentrated human red blood corpusclesMethod of preparation:

Blood (fresh) centrifugation 40% of fluid of total volume is removed from the supernatant

It must be of suitable viscosity for administration [If with high viscosity use BSWFI (Bacteriostatic sterile water for injection)]

Storage: Preparation should be packed in glass bottles and

used within 12 hr of preparation to avoid the risk of bacterial contamination

C. Fresh frozen plasma

Method of preparation: Blood (fresh) After few hrs. of collection make high

speed centrifugation plasma Stored in frozen state below -30°C. Before used it must be immersed in water bath at 37°C for about 45 min.

Here not sterilized as taken from sterile blood & prepared under aseptic conditions

Uses: Treatment of minor hemorrhage

D. Dried human plasma

Method of preparation: Plasma is difficult to filter and It is not practicable to

sterilize it by filtration but Freeze - drying [Lyophlization] is a suitable method.

State: The dried plasma is a light to deep, cream - colored powder.

It is reconstituted to the original volume with sterile water for injection at room temperature in about 10 min.

Uses: Treatment of patients suffering from burns, scales, crash

injuries.Storage:

Below 50°C protected from light.

E. Dried human fibrinogen

Method of preparation: Plasma Ethanol at 0°C & PH 7 Fibrinogen ppt. [as

least soluble] It is the least soluble one of plasma proteins.

Further purification by centrifugation. Deposit is dissolved in citrate saline solution, As

citrate bind Ca2- ions and prevent spontaneous clotting of the product.

The solution is frozen and dried White powder. It is reconstituted using sterile water for injection

before use.

E. Dried human fibrinogen

Uses: For treatment of fibrinogen deficiency, associated with

pregnancy. Repair severed nerves (plastic surgery) Aid in adhesion of grafts (skin graft)

Storage: Below 25°C protected from light.

Administration Methods

A. Gravity Flow

The majority of infusion are administrated by the gravity method.

In this method the container must be supported above the patient in order for the solution to flow

A. Gravity Flow

Flow will not begin until the pinch clamp is opened and air is allowed to enter the container (For a plastic infusion container, however, air is not required in order for the solution to flow)

The rate can be adjusted by counting the drops that enter the drip chamber & The clamp on the tubing is then adjusted to regulate flow.

However, Crass and Vane: reported that intravenous fluid delivery via gravity-flow I.V. infusion system is highly inaccurate so to ensure appropriate fluid delivery, better monitoring or improvement of I.V. fluid administration systems or the use of electronic infusion control devices is recommended.

B. Piggyback Administration

Piggyback administration is a method of I.V. administration by which solution from two containers flow into the patient's vein through common tubing and a common injection silence (vein-puncture )

One solution generally is a large-volume parenteral for continuous infusion and is sometimes designated as the primary solution.

B. Piggyback Administration The other solution Is usually an Intermittent,

Infusion such as an antibiotic, that may be referred to as the secondary, or piggyback, solution.

The piggyback solution is most frequently 50 or 100 ml of 5% dextrose injection or 0.9% sodium chloride injection (act as vehicle for the 2nd drug)

The piggyback container may be a glass bottle or a plastic container referred to as a mini bottle Mini-Bag container

B. Piggyback Administration The primary solution container and the piggyback

solution container are connected in a "Y" type tube

A continuous, straight administration set connects the primary solution container to the patient

This set has a "Y" injection site for the attachment of a second administration set, which connects to the piggyback solution container.

B. Piggyback Administration The use of these two sets together allows for the

efficient, safe administration of piggyback solutions. First, the primary solution drip rail is established

At the appropriate time, the clamp to the piggyback set can be opened to allow the piggyback solution to flow through the tubing.

Because the piggyback solution is hanging higher the primary solution, the greater pressure allows it to flow in preference to the primary solution

B. Piggyback Administration The piggyback solution is prevented from (lowing

up and into the primary solution container by a one-way check valve on the primary set This check valve allows the solution to flow from the primary bottle the patient, but not the opposite way.

Used for administration of some drugs that can't be admixtured due to delayed type incompatibilities 

Alternative system In some types we can discard the use of mini piggy bags by injection of the 2nd drug [intermittent] in the dripping chamber at certain predetermined times.

C. Pumps and controllers

There are different types of pumps such as: Syringe pumps Peristaltic pumps Volumetric pumps

Volumetric pumps will be used as an aid for the infusion of the following types of solutions:

Parenteral nutrient (hyper-alimentation liquids or TPN) Low-dose insulin infusion Lidocaine drips Dopamine Heparin infusion

C. Pumps and controllers

(cont.) Volumetric pumps will be used as an aid for the infusion of the following types of solutions:

Intravenous fatsSmall volume administration

Nitroprusside Magnesium infusion Blood (emergency only) Elemental diets [so used for certain drugs]

Syringe-pump infusion & Peristaltic pumps are of limited use

Thank you!For your time.