Biologics

Question 1

Size of generic molecules, insulin, growth hormone and monoclonal antibody

Answer 1

Generic molecules - 200 daltons
Insulin - 5,808 daltons
Growth hormone - 22,000 daltons
Monoclonal antibody - 150,000 daltons

Question 2

How are biologics usually made?

Answer 2

Most biological medicines are made by biotechnology, often using sophisticated cell systems and recombinant DNA technology.
The relevant target gene is cloned and transferred to a host cell (usually Chinese hamster ovary cells) to produce large quantities of the required monoclonal antibody or complex protein.

Question 3

When the active substance is a protein, how must the biosimilar and reference medicine be the same?

Answer 3

They must contain the same protein (i.e. amino acid sequence) and the same ‘3D’ structure (folding of the protein). Amino acid sequence and folding are the main factors that determine biological activity.
They must have the same posology and route of administration. Some differences may
be allowed e.g. excipients, presentation (e.g. powder to be reconstituted versus solution ready for injection) and administration device (e.g. type of delivery pen).

Question 4

Types I hypersensitivity reactions

Answer 4

Type I includes urticaria, hayfever, asthma, angioedema and ANAPHYLAXIS (specific type of antibody, immunoglobulin E (IgE), recognises a foreign antigen and attaches itself to it).

Question 5

Type II hypersensitivity reactions

Answer 5

AUTOIMMUNE reactions, are due to the abnormal binding of antibodies to normal host targets. Autoimmune diseases involve immunoglobulin G (IgG) and M (IgM) antibodies that activate the complement cascade. This causes inflammation and damage to tissues.

Question 6

Type III hypersensitivity reactions

Answer 6

Type III hypersensitivity reaction involves IgG antibodies bound to foreign antigens in the blood. These antibody–antigen complexes can precipitate and get stuck in certain locations, such as blood vessels in the skin, kidneys and joints, where they activate the complement cascade to cause local damage.

Common cutaneous examples of type III hypersensitivity reactions include:
Henoch–Schönlein purpura
Small-vessel vasculitis
Systemic lupus erythematosus
Rheumatoid arthritis
Serum sickness.
Most commonly, immune-complex reactions cause palpable purpura, the hallmark of small-vessel vasculitis. These are visible, non-blanching haemorrhages that are raised and palpable on examination.

Question 7

Type IV hypersensitivity reactions

Answer 7

DELAYED hypersensitivity reaction occurs 48–72 hours after exposure to the allergen. This reaction does not involve antibodies. Instead, eosinophils, monocytes, or lymphocytes called T cells are activated by the antigen. The helper CD4+ T cells initially recognise the antigen, releasing cytokines that activate the immune system with killer CD8+ T cells to destroy the target cells on contact, and macrophages to wall off the antigen and prevent further damage.

Common examples of cutaneous type IV hypersensitivity reactions include:
Allergic contact dermatitis — commonly to hair dye, nickel in jewellery, poison ivy
The Mantoux test (used to detect active tuberculosis)
Delayed drug reactions, including:
Morbilliform drug reactions
Drug hypersensitivity syndrome (formerly known as DRESS)
Erythema multiforme
Lichenoid drug eruptions
SJS / TEN